MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Current Alzheimer Research' source. Wed, 08 Feb 2012 20:43:03 +0100 http://www.medworm.com/index.php?rid=5539694&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22191563%26dopt%3DAbstract In this study, twenty five amnestic MCI patients and 25 healthy controls underwent structural MRI and comprehensive neuropsychological assessment. The groups' grey matter volumes were compared with voxel based morphometry and were also correlated with scores obtained on paired associates learning and category fluency tasks. MCI patients had significantly reduced grey matter volume in left mediotemporal and other neocortical regions compared to controls. Atrophy in perirhinal and anterior inferior temporal cortex was associated with poor scores on both category fluency and paired associates learning tasks. After 36 months, 44% of the MCI sample converted to dementia. Converter and non-converter MCI subgroups differed in paired associates learning and in category fluency scores, and showed l... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5539694 Sun, 25 Dec 2011 17:06:37 +0100 5539694 http://www.medworm.com/index.php?rid=5539693&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22191564%26dopt%3DAbstract Authors: Spulber G, Niskanen E, Macdonald S, Kivipelto M, Padilla D, Julkunen V, Hallikainen M, Vanninen R, Wahlund LO, Soininen H Abstract Mild cognitive impairment (MCI) often represents a prodromal form of dementia, conferring a significantly higher risk of converting to probable Alzheimer's disease (AD). The aim of this study is to characterise the differences of grey matter (GM) distribution and dynamics between progressive and stable MCI subjects during a 2 year period preceding the conversion to AD. We included 48 stable MCI and 12 progressive MCI cases based on the availability of 3 serial scans acquired with approximately 1 year scan interval. For the progressive MCI group, the third scan was acquired at the time of the clinical diagnosis of AD, while the first two scans w... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5539693 Sun, 25 Dec 2011 17:06:29 +0100 5539693 http://www.medworm.com/index.php?rid=5539692&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22191565%26dopt%3DAbstract Authors: Nielsen HM, Palmqvist S, Minthon L, Londos E, Wennström M Abstract Numerous reports over the years have described neuroinflammatory events and vascular changes in neurodegenerative diseases such as Alzheimers disease (AD) and dementia with Lewy bodies (DLB). Interestingly, recent reports from other research areas suggest that the inflammatory and vascular processes are influenced by gender. These findings are intriguing from the perspective that women show a higher incidence of AD and warrant investigations on how gender influences various processes in neurodegenerative dementia. In the current study we measured the cerebrospinal fluid (CSF) and plasma concentrations of hyaluroinic acid (HA), an adhesionmolecule known to regulate both vascular and inflammatory processes, ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5539692 Sun, 25 Dec 2011 17:06:19 +0100 5539692 http://www.medworm.com/index.php?rid=5539691&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22191566%26dopt%3DAbstract Authors: Barbash S, Soreq H Abstract End-stage Alzheimer`s disease (AD) involves drastic modifications in neuronal molecular and cellular processes, but little is known about the dynamics of these modifications during disease initiation and progression. Here, we report meta-analysis of 100 publicly available Microarray datasets using threshold-independent analysis. We found that different patients react to AD progression by variable single transcript alterations which however lead to similar changes in functional gene groups. Stratification by patients' cognitive deterioration presented hippocampal-specific mRNA alterations which involved progressively changed gene categories and indicate changes in epigenetic state and microRNA profiles. In addition, datasets from laser-captured n... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5539691 Sun, 25 Dec 2011 17:06:11 +0100 5539691 http://www.medworm.com/index.php?rid=5516919&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22171951%26dopt%3DAbstract Authors: Zheng Y, Balabhadrapatruni S, Masumura C, Darlington CL, Smith PF Abstract Ampakines are a class of putative nootropic drug designed to positively modulate the AMPA receptor and have been investigated as a potential treatment for cognitive disorders such as Alzheimer's Disease. Nonetheless, some ampakines such as CX717 have been incompletely characterized in behavioural pharmacological studies. Therefore, in this study, we attempted to further characterize the effects of the ampakine, CX717 (20 mg/kg s.c), on the performance of rats in a 5 choice serial reaction time (5CSRTT) and object recognition memory task, using rats with cognitive deficits caused by bilateral vestibular deafferentation (BVD) as a model. In the 5CSRTT, when the stimulus duration was varied from 5 to 2... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5516919 Thu, 01 Dec 2011 05:00:00 +0100 5516919 http://www.medworm.com/index.php?rid=5516918&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22171952%26dopt%3DAbstract Authors: Kiryk A, Mochol G, Filipkowski RK, Wawrzyniak M, Lioudyno V, Knapska E, Gorkiewicz T, Balcerzyk M, Leski S, Leuven FV, Lipp HP, Wojcik DK, Kaczmarek L Abstract In the present study, we used a new training paradigm in the intelliCage automatic behavioral assessment system to investigate cognitive functions of the transgenic mice harboring London mutation of the human amyloid precursor protein (APP.V717I). Three groups of animals: 5-, 12- and 18-24-month old were subjected to both Water Maze training and the IntelliCage-based appetitive conditioning. The spatial memory deficit was observed in all three groups of transgenic mice in both behavioral paradigms. However, the APP mice were capable to learn normally when co-housed with the wild-type (WT) littermates, in contrast to... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5516918 Thu, 01 Dec 2011 05:00:00 +0100 5516918 http://www.medworm.com/index.php?rid=5383709&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22044023%26dopt%3DAbstract We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4±3.6, range 13-28 points) with incipient (n=11) and probable (n=36) AD underwent positron emission tomography with [(18)F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ(1-42), p-tau(181), and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole sample (n=47) and for the subgroups stratified as mild (MMSE >20 points, n=30) and moderate (MMSE <21 points, n=17) AD. In the whole patient sample, the agreement with the FDG-PET finding was 77% (chance-corrected kappa [κ]=0.34, p=0.016) for t-tau, 68% (κ=0.10, n.s.) for p-tau(18... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5383709 Wed, 26 Oct 2011 04:00:00 +0100 5383709 http://www.medworm.com/index.php?rid=5383708&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22044024%26dopt%3DAbstract Authors: Colom LV, Castaneda MT, Hernandez S, Perry G, Jaime S, Touhami A Abstract Alzheimer's disease (AD) is a devastating disorder that leads to memory loss and dementia. Neurodegeneration of cholinergic neurons in the septum and other basal forebrain areas is evident in early stages of AD. Glutamatergic neurons are also affected early in AD. In these stages, amyloid-β-peptide (Aβ) plaques are present in the hippocampus and other cortices but not in the basal forebrain, which includes the septum. We postulate that early deposition of hippocampal Aβ damages the axon terminals of cholinergic and glutamatergic septo-hippocampal neurons, leading to their degeneration. To determine the mechanisms underlying septal degeneration, fibrillar Aβ1-40 was injected into the Cornu Ammonis... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5383708 Wed, 26 Oct 2011 04:00:00 +0100 5383708 http://www.medworm.com/index.php?rid=5383707&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22044025%26dopt%3DAbstract We examined the regulation of cellular CaM levels in AD lymphoblasts. An elevated CaM content in AD cells was found when compared with control cells from age-matched individuals. We did not find significant differences in the expression of the three genes that encode CaM: CALM1, 2, 3, by real time RT-PCR. However, we observed that the half-life of CaM was higher in lymphoblasts from AD than in control cells, suggesting that degradation of CaM is impaired in AD lymphoblasts. The rate of CaM degradation was found to be dependent on cellular Ca(2+) and ROS levels. CaM degradation occurs mainly via the ubiquitin-proteasome system. Increased levels of CaM were associated with overactivation of PI3K/Akt and CaMKII. Our results suggest that increased levels of CaM synergize with serum to overacti... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5383707 Wed, 26 Oct 2011 04:00:00 +0100 5383707 http://www.medworm.com/index.php?rid=5383706&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22044026%26dopt%3DAbstract Authors: Olgiati P, Politis A, Albani D, Rodilossi S, Polito L, Ateri E, Zisaki A, Piperi C, Liappas I, Stamouli E, Mailis A, Atti A, Ferrari B, Morini V, Moretti F, Biella G, Forloni G, Papadimitriou G, De Ronchi D, Kalofoutis A, Serretti A Abstract The pathophysiology of Alzheimer's disease (AD) is influenced by sorting-protein related receptor (sorLa) that is less expressed in AD patients. The gene encoding sorLa (SORL1) has been investigated as a susceptibility factor for late-onset AD (LOAD) with conflicting results. Our objectives were to confirm the association between SORL1 SNPs and LOAD in two independent South-European centers and to perform a mega-analysis of published samples. We analyzed three SORL1 SNPs (intron 6: rs668387; rs689021; rs641120) from the Greece-Italy Ge... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5383706 Wed, 26 Oct 2011 04:00:00 +0100 5383706 http://www.medworm.com/index.php?rid=5383705&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22044027%26dopt%3DAbstract Authors: Yang ZZ, Zhang YQ, Wu K, Wang ZZ, Qi XR Abstract The aim of the study was mainly to investigate the relationship between concentration of rivastigmine and its inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) following intranasal (IN) and intravenous (IV) administration in rats, and to provide a novel nasal delivery route for the brain disease therapy. Rivastigmine was administered to male rats at 2 mg/kg by IN and IV route. Drug concentration, AChE and BuChE activity were measured in the plasma, central nervous system (CNS) regions i.e. olfactory region, hippocampus, cerebrum and cerebellum, and peripheral tissues. It was determined that rivastigmine was characterized by extremely rapid and complete absorption into the systemic circulation follow... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5383705 Wed, 26 Oct 2011 04:00:00 +0100 5383705 http://www.medworm.com/index.php?rid=5180534&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21875407%26dopt%3DAbstract Authors: Olivares D, Deshpande VK, Shi Y, Lahiri DK, Greig NH, Rogers JT, Huang X Abstract Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR), approved for moderate to severe Alzheimer's disease (AD) treatment within the US and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and Ebixa and Abixa (Lundbeck), may have potential in alleviating additional neurological conditions, such as vascular dementia (VD) and Parkinson's disease (PD). In various animal models, memantine has been reported to be a neuroprotective agent that positively impacts both neurodegenerative and vascular processes. While excessive levels of glutamate result in neurotoxicity, in part through the over-activation of NMDARs, memantine-as a partial NMDAR antagonist, blocks... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5180534 Mon, 29 Aug 2011 23:00:00 +0100 5180534 http://www.medworm.com/index.php?rid=5180533&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21875408%26dopt%3DAbstract Authors: Douglas Shytle R, Tan J, Bickford PC, Rezai-Zadeh K, Hou L, Zeng J, Sanberg PR, Sanberg CD, Alberte RS, Fink RC, Roschek B Abstract In a previous in vitro study, the standardized turmeric extract, HSS-888, showed strong inhibition of Aβ aggregation and secretion in vitro, indicating that HSS-888 might be therapeutically important. Therefore, in the present study, HSS-888 was evaluated in vivo using transgenic 'Alzheimer' mice (Tg2576) over-expressing Aβ protein. Following a six-month prevention period where mice received extract HSS-888 (5mg/mouse/day), tetrahydrocurcumin (THC) or a control through ingestion of customized animal feed pellets (0.1% w/w treatment), HSS-888 significantly reduced brain levels of soluble (~40%) and insoluble (~20%) Aβ as well as phosphorylat... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5180533 Mon, 29 Aug 2011 23:00:00 +0100 5180533 http://www.medworm.com/index.php?rid=5180532&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21875409%26dopt%3DAbstract Authors: Hochstrasser T, Ehrlich D, Marksteiner J, Sperner-Unterweger B, Humpel C Abstract Alzheimer's disease (AD) is the most prevalent type of dementia. Despite considerable advances in diagnostic accuracy, diagnostic procedures that are easily accessible are still sorely needed. Blood biomarkers are therefore in the focus of research. Platelets contain a high concentration of the amyloid precursor protein (APP), which has been mentioned as a potentially useful diagnostic marker. The aim of the present study was to analyze various cell adhesion molecules (CAMs), cytokines, growth factors, and matrix metalloproteinases (MMPs) in platelets of AD and mild cognitively impaired (MCI) patients as compared to healthy controls. Our data show a significant decrease in the levels of epide... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5180532 Mon, 29 Aug 2011 23:00:00 +0100 5180532 http://www.medworm.com/index.php?rid=5180531&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21875410%26dopt%3DAbstract Authors: Straten G, Saur R, Laske C, Gasser T, Annas P, Basun H, Leyhe T Abstract Preclinical and clinical studies gave evidence that lithium could be useful in the treatment of Alzheimer's disease (AD). One possible mechanism of action might be the induction of neurotrophins. Recently, we found a significant increase of brain-derived neurotrophic factor (BDNF) serum levels in AD patients treated with lithium and a significant decrease of ADAS Cog sum scores in comparison to placebo-treated patients. In another previous study we have shown that glial cell line-derived neurotrophic factor (GDNF) levels in CSF of patients with early AD are increased most probably due to an upregulated expression in CNS as an adaptive process of the impaired brain to enhance neurotrophic support at le... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5180531 Mon, 29 Aug 2011 23:00:00 +0100 5180531 http://www.medworm.com/index.php?rid=5180530&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21875411%26dopt%3DAbstract Authors: Bosch MN, Pugliese M, Gimeno-Bayón J, Rodríguez MJ, Mahy N Abstract In the search for appropriate models for Alzheimer's disease (AD) involving animals other than rodents, several laboratories are working with animals that naturally develop cognitive dysfunction. Among the animals tested, dogs are quite unique in helping to elucidate the cascade of events that take place in brain amyloid-beta (Aβ) deposition aging, and cognitive deficit. Recent innovative research has validated human methods and tools for the analysis of canine neuropathology and has allowed the development of two different approaches to investigate dogs as natural models of AD. The first approach relates AD-like neuropathy with the decline in memory and learning ability in aged housed dogs in a highly ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5180530 Mon, 29 Aug 2011 23:00:00 +0100 5180530 http://www.medworm.com/index.php?rid=5180529&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21875412%26dopt%3DAbstract Authors: Ceyhan E, Beg MF, Ceritoǧlu C, Wang L, Morris JC, Csernansky JG, Miller MI, Ratnanather JT Abstract In this article, we use longitudinal morphometry (shape and size) measures of hippocampus in subjects with mild dementia of Alzheimer type (DAT) and nondemented controls in logistic discrimination. The morphometric measures we use are volume and metric distance measures at baseline and follow-up (two years apart from baseline). Morphometric differences with respect to a template hippocampus were measured by the metric distance obtained from the large deformation diffeomorphic metric mapping (LDDMM) algorithm. LDDMM assigns metric distances on the space of anatomical images, thereby allowing for the direct comparison and quantization of morphometric changes. We also apply pr... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5180529 Mon, 29 Aug 2011 23:00:00 +0100 5180529 http://www.medworm.com/index.php?rid=5118314&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21827396%26dopt%3DAbstract Authors: Maccioni RB PMID: 21827396 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5118314 Mon, 08 Aug 2011 23:00:00 +0100 5118314 http://www.medworm.com/index.php?rid=5022864&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707533%26dopt%3DAbstract Authors: Gaudig M, Richarz U, Han J, Baelen BV, Schäuble B To evaluate the effects of galantamine withdrawal, and compare this with uninterrupted therapy, two 6-week double-blind withdrawal studies (Studies 1 and 2) were performed. These enrolled individuals who had completed one of two 3- or 5-month randomized clinical trials (parent trials) involving patients with mild to moderate Alzheimer's disease (AD). In Study 1 (GAL-USA-11; n=723), patients continuously treated with galantamine 16 mg/day exhibited a mean (± standard error [SE]) improvement in 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale score of 1.8 (± 0.46) points at Week 6 compared with the parent trial baseline, (p<0.001 vs placebo; observed cases analysis). Over the same period, patients swit... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=5022864 Sun, 26 Jun 2011 23:00:00 +0100 5022864 http://www.medworm.com/index.php?rid=4973312&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679154%26dopt%3DAbstract Authors: Boutajangout A, Sigurdsson EM, Krishnamurthy PK Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of Alzheimer's disease (AD) and are primarily composed of aggregates of hyperphosphorylated forms of the microtubule associated protein tau. It is likely that an imbalance of kinase and phosphatase activities leads to the abnormal phosphorylation of tau and subsequent aggregation. The wide ranging therapeutic approaches that are being developed include to inhibit tau kinases, to enhance phosphatase activity, to promote microtubule stability, and to reduce tau aggregate formation and/or enhance their clearance with small molecule drugs or by immunotherapeutic means. Most of these promising approaches are still in preclinical development whilst some have progresse... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4973312 Thu, 16 Jun 2011 23:00:00 +0100 4973312 http://www.medworm.com/index.php?rid=4973311&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679155%26dopt%3DAbstract Authors: Ramassamy C, Belkacémi A PMID: 21679155 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4973311 Thu, 16 Jun 2011 23:00:00 +0100 4973311 http://www.medworm.com/index.php?rid=4973310&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679156%26dopt%3DAbstract Authors: Antón Alvarez X, Cacabelos R, Sampedro C, Couceiro V, Aleixandre M, Vargas M, Linares C, Granizo E, García-Fantini M, Baurecht W, Doppler E, Moessler H Treatment with neurotrophic agents might enhance and/or prolong the effects of cholinesterase inhibitors (ChEIs) in Alzheimer's disease (AD). We compared the safety and efficacy of the neurotrophic compound Cerebrolysin (10 ml; n=64), donepezil (10 mg; n=66) and a combination of both treatments (n=67) in mild-to-moderate (mini-mental state examination-MMSE score 12-25) probable AD patients enrolled in a randomized, double-blind trial. Primary endpoints were global outcome (Clinician's Interview-Based Impression of Change plus caregiver input; CIBIC+) and cognition (change from baseline in AD Assessment Scale-cognitive subscal... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4973310 Thu, 16 Jun 2011 23:00:00 +0100 4973310 http://www.medworm.com/index.php?rid=4925256&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21619517%26dopt%3DAbstract Conclusions: Midlife metabolic diseases, especially diabetes, are independently associated with impaired cognition in old age. Even a more subtle weight change than suggested previously was associated with lower old age cognition. There was evidence from direct causal pathway between cardiovascular disease and old age cognition, while the correlation between midlife BMI and old age cognition was explained mostly by genetic factors. Abstract: Objective: Epidemiological studies suggest a relationship between midlife metabolism and old age cognition. We examined the effect of midlife BMI and related metabolic conditions on old age cognitive performance and whether there was evidence from direct causal pathways behind these associations in a large sample of Finnish twins. Design: Midlife varia... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4925256 Thu, 26 May 2011 23:00:00 +0100 4925256 http://www.medworm.com/index.php?rid=4878716&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605061%26dopt%3DAbstract In this study, we examined the ability of tolfenamic acid to cross the blood brain barrier (BBB) by predicting its logBB and logPS values, the indexes of BBB permeability, using computational models. We also determined, via in vitro methods, the brain penetration capacity factor [(KIAM/MW4)x1010] using phosphatidylcholine column chromatography. The obtained logBB, logPS and (KIAM/MW4)x1010 values predicted that tolfenamic acid can passively transfer into the central nervous system (CNS). These results were validated in vivo using LC-MS analysis after administration of tolfenamic acid intravenously to guinea pigs and mice. The present study provides the first evidence of the ability of tolfenamic acid to cross the BBB and offers a comparative analysis of approaches used to predict the abili... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878716 Mon, 23 May 2011 23:00:00 +0100 4878716 http://www.medworm.com/index.php?rid=4878715&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605062%26dopt%3DAbstract Authors: Fleming JL, Phiel CJ, Toland AE Alzheimer's disease (AD) is a common, progressive neurodegenerative disorder without highly effective therapies. The etiology of AD is heterogeneous with amyloid-beta plaques, neurofibrillary tangles, oxidative stress, and aberrant DNA methylation all implicated in the disease pathogenesis. DNA methylation is a well-established process for regulating gene expression and has been found to regulate a growing number of important genes involved in AD development and progression. Additionally, aberrations in one-carbon metabolism are a common finding in AD patients with individuals exhibiting low S-adenosylmethionine and high homocysteine levels as well as low folate and vitamin B. Oxidative stress is considered one of the earliest events in AD patho... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878715 Mon, 23 May 2011 23:00:00 +0100 4878715 http://www.medworm.com/index.php?rid=4878714&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605063%26dopt%3DAbstract Authors: Huang Y, Zheng L, Halliday G, Dobson-Stone C, Wang Y, Tang HD, Cao L, Deng YL, Wang G, Zhang YM, Wang JH, Hallupp M, Kwok J, Chen SD Apolipoprotein E (APOE) ε4 allele and sigma-1 receptor (SIGMAR1) c.5C (Q2P) polymorphisms have been acknowledged as risk factors for developing Alzheimer's disease (AD). However, whether these polymorphisms influence the disease process is unclear. Therefore, two cohorts with a clinical diagnosis of AD were recruited, a postmortem confirmed Australian cohort (82 cases) from the Australian Brain Bank Network, and a Chinese cohort with detailed clinical assessments recruited through an epidemiology study in Shanghai and through the neurology department outpatients clinic of Shanghai Ruijin Hospital (330 cases). SIGMAR1 Q2P and APOE genotyping was ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878714 Mon, 23 May 2011 23:00:00 +0100 4878714 http://www.medworm.com/index.php?rid=4878713&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605064%26dopt%3DAbstract Authors: Woolley JD, Strobl EV, Shelly WB, Miller BL, Mellon SH, Rankin KP Brain-derived neurotrophic factor (BDNF) is a growth factor implicated in neuronal survival. Studies have reported altered BDNF serum concentrations in patients with Alzheimer's disease. However, these studies have been inconsistent. Few studies have investigated BDNF concentrations across multiple neurodegenerative diseases, and no studies have investigated BDNF concentrations in patients with frontotemporal dementia. To examine BDNF concentrations in different neurodegenerative diseases, we measured serum concentrations of BDNF using enzyme-linked immunoassay in subjects with behavioral-variant frontotemporal dementia (bvFTD, n=20), semantic dementia (SemD, n=16), AD (n=34), and mild cognitive impairment (MCI,... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878713 Mon, 23 May 2011 23:00:00 +0100 4878713 http://www.medworm.com/index.php?rid=4878748&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605029%26dopt%3DAbstract Authors: Wang Z, Yang L, Zheng H Alzheimer's disease (AD) is the most common cause of dementia in aging populations. Although amyloid plaques are the hallmark of AD, loss of synapses and synaptic dysfunction are closely associated with the duration and severity of cognitive impairment in AD patients. Amyloid precursor protein (APP) and its cleavage products including Aβ have been suggested as homeostatic regulators of synaptic activity. APP manipulation and Aβ application, in vitro and in vivo, affect synapse formation and synaptic transmission. Moreover, synaptic dysfunction and learning deficits precede Aβ plaque deposition, suggesting that synaptic alterations may underlie the initial development of the disease. Because of the pivotal role of APP and Aβ in AD pathogenesis, it is... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878748 Sun, 22 May 2011 23:00:00 +0100 4878748 http://www.medworm.com/index.php?rid=4878747&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605030%26dopt%3DAbstract Authors: Walter J factor for late onset Alzheimer's disease (AD). Apo E is the major component of lipoprotein particles in the brain that mediate transport of cholesterol and other lipids between neurons and glial cells, indicating an implication of cerebral lipid metabolism in the pathogenesis of AD. In addition, apo E is also involved in the metabolism and aggregation of the amyloid β-peptide (Aβ) that derives from proteolytic processing of the amyloid precursor protein (APP) and is found in plaques of AD brains. The generation of Aβ involves sequential cleavages of APP by proteases called β- and γ-secretase. γ-Secretase is a high molecular weight protein complex containing presenilins as catalytically active subunits. Importantly, mutations in the genes of APP and the two homo... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878747 Sun, 22 May 2011 23:00:00 +0100 4878747 http://www.medworm.com/index.php?rid=4878746&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605031%26dopt%3DAbstract Authors: Vincent B, Checler F Proteases regulate numerous physiological functions in all living organisms. Because, of their contribution to βAPP processing, α-, β- and γ-secretases have focused particular attention of researchers in the field of Alzheimer's disease (AD) during the past 20 years. Whereas the β-secretase BACE1 and the heterotetrameric presenilin-dependent γ-secretase complex were identified between 1995 and 2002, α-secretase activity was attributed to previously described ADAM10 and ADAM17, two members of the type I integral membrane protein family called ADAMs (A Disintegrin And Metalloprotease). ADAM10 and/or ADAM17 target numerous substrates through various modes of action. This review focuses on the complex physiology of these α-secretases and will document ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878746 Sun, 22 May 2011 23:00:00 +0100 4878746 http://www.medworm.com/index.php?rid=4878744&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605032%26dopt%3DAbstract Authors: Sato C, Zhao G, Ilagan MX The Notch pathway is a critical mediator of short-range cell-cell communication that is reiteratively used to regulate a diverse array of cellular processes during embryonic development and the renewal and maintenance of adult tissues. Most Notch-dependent processes utilize a core signaling mechanism that is dependent on regulated intramembrane proteolysis: Upon ligand binding, Notch receptors undergo ectodomain shedding by ADAM metalloproteases, followed by γ-secretase-mediated intramembrane proteolysis. This releases the Notch intracellular domain, which translocates to the nucleus to activate transcription. In this review, we highlight the roles of Notch signaling particularly in self-renewing tissues in adults and several human diseases and raise... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878744 Sun, 22 May 2011 23:00:00 +0100 4878744 http://www.medworm.com/index.php?rid=4878743&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605033%26dopt%3DAbstract Authors: Lichtenthaler SF α-secretase is the name for a metalloprotease activity, which is assumed to play a key role in the prevention of the molecular mechanisms underlying Alzheimer's disease (AD). Proteases similar to α- secretase are essential for a wide range of biological processes, such as cell adhesion and embryonic development. The molecular culprit in AD is the amyloid β peptide (Aβ), which derives from the amyloid precursor protein (APP) through sequential cleavage by the two proteases β and γ-secretase. In contrast, α-secretase, which is the metalloprotease ADAM10, cleaves APP within the Aβ domain, thus preventing Aβ generation. Additionally, it produces a secreted APP ectodomain with neurotrophic and neuroprotective properties. An increase in α-secretase cleavag... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878743 Sun, 22 May 2011 23:00:00 +0100 4878743 http://www.medworm.com/index.php?rid=4878741&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605034%26dopt%3DAbstract Authors: Fleck D, Garratt AN, Haass C, Willem M Neuregulin-1 (NRG1), which is also called acetylcholine receptor inducing activity (ARIA) or glial growth factor (GGF), signals as a ligand of ErbB receptors in a variety of important developmental processes but also later in life. NRG1 mediated signaling is crucial for cardiogenesis and the development of the breast. In the nervous system, NRG1 functions are essential for peripheral myelination, the establishment and maintenance of neuromuscular and sensorimotoric systems as well as for the plasticity of cortical neuronal circuits. There is strong evidence that deregulation of NRG1 is involved in breast cancer and schizophrenia. Many splice variants of NRG1 are expressed in the brain and all contain an EGF-like domain, which exerts the N... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878741 Sun, 22 May 2011 23:00:00 +0100 4878741 http://www.medworm.com/index.php?rid=4878739&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605035%26dopt%3DAbstract Authors: Konietzko U Altered proteolytic processing of the β-amyloid precursor protein (APP) is a central event in familial and sporadic Alzheimer's disease (AD). In a process termed regulated intramembrane proteolysis (RIP), APP first undergoes ectodomain shedding executed either by α- secretases at the plasma membrane or by β-secretase in the endosomal compartment. The remaining membrane-anchored stubs are cleaved within the membrane plane by the γ-secretase complex, releasing the APP intracellular domain (AICD) into the cytosol and leading to the generation of the Aβ peptide in the amyloidogenic pathway that is initiated by β-secretase. The Aβ peptides aggregate to form soluble oligomers and finally deposit into amyloid plaques that are a hallmark of AD. Recent evidence indic... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878739 Sun, 22 May 2011 23:00:00 +0100 4878739 http://www.medworm.com/index.php?rid=4878737&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605036%26dopt%3DAbstract Authors: Endres K, Fahrenholz F ADAM10 (A disintegrin and metalloproteinase 10) has been demonstrated as an enzyme with protective properties in Alzheimer's disease: in mouse models it not only lowered generation of toxic A-beta peptides and formation of senile plaques but also alleviated learning deficits and enhanced synaptic density. This is due to cleavage of the amyloid precursor protein (APP) within its A-beta stretch and to the release of the extracellular domain of APP with neuroprotective function. Aside from cleaving APP, ADAM10 has been linked to over 40 putative substrates at least in cell culture. These substrates are connected with important cellular functions such as cell migration, stress response and transport. For this contribution we focussed on ADAM10 acting on the ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878737 Sun, 22 May 2011 23:00:00 +0100 4878737 http://www.medworm.com/index.php?rid=4878736&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605037%26dopt%3DAbstract Authors: Fuentes P, Catalan J Alzheimer's Disease (AD) physiopathology is not yet totally established. Nevertheless it is known that a metabolism dysfunction of the amyloid beta precursor protein (APP) and the abnormal tau protein phosphorylation lead to the formation of neuritic plaques and neurofibrillary tangles, respectively. These events finally drive to the clinical expression of dementia. Formally approved during the past decade, treatments for AD are lacking of an updating, being essentially symptomatic. Anticholinesterase agents have failed in providing a substantial improvement in the mental health condition of AD patients. On the other hand, antiamyloid strategies, have failed in their efficacy or security on their last development phases. In this context, tau represents a p... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878736 Sun, 22 May 2011 23:00:00 +0100 4878736 http://www.medworm.com/index.php?rid=4878735&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605038%26dopt%3DAbstract Authors: Navarrete LP, Pérez P, Morales I, Maccioni RB The anomalous aggregation of proteins into pathological filaments is a common feature of a many human diseases, often related to aging. In this context, neurodegenerative pathologies such as Alzheimer's disease (AD) account for a major part of these protein misfolding diseases. AD is characterized by pathological aggregation of two proteins, tau and Ab-amyloid. The intracellular neurofibrillary tangles (NFTs) and neuropil threads consists of filaments of the modified microtubule-associated protein tau, while extracellular amyloid plaques consists of filaments of Ab-peptide. It is noteworthy that tau oligomers with a prefilamentous structure appear to play a role at early stages of AD and tauopathies, but also in asymptomatic patie... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878735 Sun, 22 May 2011 23:00:00 +0100 4878735 http://www.medworm.com/index.php?rid=4878734&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605039%26dopt%3DAbstract Authors: Lasagna-Reeves CA, Castillo-Carranza DL, Jackson GR, Kayed R The aggregation and accumulation of the microtubule-associated protein (Tau) is a pathological hallmark of Alzheimer's disease (AD) and many neurodegenerative diseases. For a long time research has focused on neurofibrillary tangles (NFTs) and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. The correlation between these structures and disease progression produced conflicting results, moreover the mechanism of their formation remains poorly understood. Lately, the significance and toxicity of NFTs have been challenged and new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD; specifically, aggregates ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878734 Sun, 22 May 2011 23:00:00 +0100 4878734 http://www.medworm.com/index.php?rid=4878733&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605040%26dopt%3DAbstract Authors: Rojo LE, Gaspar P, Maccioni RB A major limitation in finding therapeutic solutions for Alzheimer's disease (AD) has been the lack of a reliable method for early diagnosis of this devastating disease. Besides the development of biomarkers in biological fluids of patients, the search for a pathology-specific neuroimaging tools is critical at the present stage in which almost 30 million people suffer this disease worldwide. Several interesting approaches have been developed, however their clinical impact has been low. One of the difficulties has been to find the proper molecular tracers to specifically tag pathognomonic lesions in AD brain, including not only amyloid aggregates but also filaments of the modified microtubule-associated protein tau. In this review, we analyze the e... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878733 Sun, 22 May 2011 23:00:00 +0100 4878733 http://www.medworm.com/index.php?rid=4878732&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605041%26dopt%3DAbstract Authors: Estrada LD, Zanlungo SM, Alvarez AR Hyperphosphorylated tau is a cardinal feature of Alzheimer's disease (AD) pathology. The deregulation of kinases that phosphorylate tau can alter normal tau-related processes, including microtubule dynamics, growth cones, and axonal transport, and induce the aggregation of tau in paired helical filaments. Here we discuss the possible roles of the Abl family of tyrosine kinases, which are essential regulators of cytoskeleton cellular signaling cascades, in AD tau pathology and how the physiological roles of Abl kinases could be connected with the cytoskeletal alterations induced by Aβ aggregates and AD progression. PMID: 21605041 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878732 Sun, 22 May 2011 23:00:00 +0100 4878732 http://www.medworm.com/index.php?rid=4878731&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605042%26dopt%3DAbstract Authors: Bonda DJ, Castellani RJ, Zhu X, Nunomura A, Lee HG, Perry G, Smith MA Mainstream thinking is dominated by the notion that the aggregation of specific proteins within neurons, and their subsequent formation into cytoplasmic and extracellular lesions, directly elicits neuronal dysfunction and death. Current dogma, for example, maintains that phosphorylated tau protein, the major component of neurofibrillary tangles, is a central mediator of disease pathogenesis. In this article, we challenge this classic notion by proposing that tau phosphorylation represents a compensatory response mounted by neurons against oxidative stress that serves a protective function. This concept provides a better understanding of the mechanisms underlying disease pathophysiology and also provides a wi... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878731 Sun, 22 May 2011 23:00:00 +0100 4878731 http://www.medworm.com/index.php?rid=4878730&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605043%26dopt%3DAbstract Authors: Belarbi K, Burnouf S, Fernandez-Gomez FJ, Desmercières J, Troquier L, Brouillette J, Tsambou L, Grosjean ME, Caillierez R, Demeyer D, Hamdane M, Schindowski K, Blum D, Buée L Alzheimer's disease (AD) is a neurodegenerative disorder histologically defined by the cerebral accumulation of amyloid deposits and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Loss of basal forebrain cholinergic neurons is another hallmark of the disease thought to contribute to the cognitive dysfunctions. To this date, the mechanisms underlying cholinergic neurons degeneration remain uncertain. The present study aimed to investigate the relationship between neurofibrillary degeneration and cholinergic defects in AD using THY-Tau22 transgenic mouse model exhibiting a major hip... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878730 Sun, 22 May 2011 23:00:00 +0100 4878730 http://www.medworm.com/index.php?rid=4878729&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605044%26dopt%3DAbstract Authors: Rudrabhatla P, Pant HC Alzheimer disease (AD) is the most common cause of dementia in adults. Aberrant hyperphosphorylation of microtubule associated protein Tau and neurofilament-M/H is one of the pathological hallmarks of AD. Most of the therapeutic strategies for treating AD are based on the inhibition of protein kinases such as glycogen synthase kinase-3β, cyclin-dependent kinase 5, and other Tau kinases. Here, we focus on protein phosphatase 2A (PP2A) as a key player in AD. PP2A expression and activity are downregulated in AD brain, contributing to the aberrant phosphorylation of Tau and NF proteins in AD. Recent data published from our lab as well as others on PP2A deregulation in AD is reviewed. The role of peptidyl prolyl isomerase Pin1 in regulation of PP2A mediated ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878729 Sun, 22 May 2011 23:00:00 +0100 4878729 http://www.medworm.com/index.php?rid=4878728&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605045%26dopt%3DAbstract Authors: Elena L, Massimo M, Alessandra B Neurodegenerative diseases termed Tauopathies, including Alzheimer disease, are characterized by the presence of intraneuronal neurofibrillary tangles (NFTs), composed by hyperphosphorylated protein Tau. Peptidyl-prolyl cis/trans isomerase Pin1 plays a pivotal role in the regulation of Tau phosphorylation/dephosphorylation state. Indeed, Pin1 specifically recognizes pThr231-Pro232 motif of Tau, catalyzes its isomerisation and, in dependence of the cellular environment, promotes its dephosphorylation by PP2A phosphatase: in the dephosphorylated state Tau is able to exert its physiological activity, promoting microtubules polymerization. However, Pin1 activity in Tauopathies in which Tau is mutated can be harmful, because the isomerase can accele... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878728 Sun, 22 May 2011 23:00:00 +0100 4878728 http://www.medworm.com/index.php?rid=4878727&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605046%26dopt%3DAbstract Authors: Farías G, Cornejo A, Jiménez J, Guzmán L, Maccioni RB Pathological tau protein aggregates can be found in brain of patients with some of the neurodegenerative diseases collectively known as tauopathies, which include Alzheimer's disease (AD). Since tau post-translational modifications including phosphorylations, glycosylations, truncation and the subsequent aggregation in oligomers, paired helical filaments (PHFs) and neurofibrillary tangles (NFTs), correlate with cognitive impairment and neurodegeneration in AD, a pathogenic role for tau and its modifications has been raised. Here we summarize the current status of knowledge about tau modifications under pathologic conditions and the evidence supporting neurotoxic - or neuroprotective - roles of the diverse forms of modifi... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878727 Sun, 22 May 2011 23:00:00 +0100 4878727 http://www.medworm.com/index.php?rid=4878726&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605047%26dopt%3DAbstract Authors: Solfrizzi V, Frisardi V, Seripa D, Logroscino G, Imbimbo BP, D'Onofrio G, Addante F, Sancarlo D, Cascavilla L, Pilotto A, Panza F There is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Only recently higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline although the Mediterranean diet (MeDi) combines several foods, micro- and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggested a... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878726 Sun, 22 May 2011 23:00:00 +0100 4878726 http://www.medworm.com/index.php?rid=4878725&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605048%26dopt%3DAbstract Authors: Gu Y, Scarmeas N Much of the attention on diet and Alzheimer's disease (AD) or cognition among the elderly has focused on the role of single nutrients or foods, while available information on dietary pattern (DP) analysis, which better reflects the complexity of the diet, is sparse. In this review, we describe different patterning approaches and present studies performed to date that have assessed the associations between DPs and risk of AD or cognitive function in the elderly. Three patterning approaches have been most commonly used: (i) hypothesis-based that use dietary quality indexes or scores (e.g. Mediterranean pattern), (ii) data-driven that use factor or cluster analysis to derive DPs, (iii) reduced rank regression which combines characteristics of the former two appro... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878725 Sun, 22 May 2011 23:00:00 +0100 4878725 http://www.medworm.com/index.php?rid=4878724&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605049%26dopt%3DAbstract In this study we have investigated the protective effects of two components of olive oil, tyrosol (Tyr) and hydroxytyrosol (OH-Tyr), against Aβ-induced toxicity. In cultured neuroblastoma N2a cells, we found that Aβ(25-35) (100µg/ml) treatment induced a decrease of glutathione (GSH) and the activation of the transcription factor NF-κB and cell death. Our results demonstrated that the number of cell death decreased when cells were co-treated with Aβ and Tyr or OH-Tyr. However, neither of these phenolic compounds was able to prevent the decrease of GSH induced by H(2)O(2) or Aβ. We found that the increase in the nuclear translocation of the NF-κB subunits after Aβ exposure was attenuated in the presence of Tyr or OH-Tyr. These results identified two individual food components of the ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878724 Sun, 22 May 2011 23:00:00 +0100 4878724 http://www.medworm.com/index.php?rid=4878723&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605050%26dopt%3DAbstract Authors: Panza F, Frisardi V, Seripa D, Imbimbo BP, Sancarlo D, D'Onofrio G, Addante F, Paris F, Pilotto A, Solfrizzi V At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important for the development of age-related cognitive decline (ARCD), mild cognitive impairment (MCI), and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). Among vascular-related factors, metabolic syndrome (MetS) has been associated with the reduced risk of predementia syndromes (ARCD and MCI), overall dement... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878723 Sun, 22 May 2011 23:00:00 +0100 4878723 http://www.medworm.com/index.php?rid=4878722&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605051%26dopt%3DAbstract Authors: Calon F The current rise in the prevalence of Alzheimer's disease (AD) is unfortunately not matched by new treatment options. In the last 10 years, epidemiological, preclinical and clinical data have enlightened the possible preventive action of omega-3 polyunsaturated fatty acids (n-3 PUFA) in AD and other diseases. While the contribution of recent studies to our general knowledge is priceless, many important new questions have been raised. In the present review, we aim at addressing some of these timely interrogations. First, the transport of n-3 PUFA across the blood-brain barrier is underscored based on preclinical data. Second, the relative contribution of two neuroactive n-3 PUFA found in fish oil, docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA, 20:5... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878722 Sun, 22 May 2011 23:00:00 +0100 4878722 http://www.medworm.com/index.php?rid=4878721&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605052%26dopt%3DAbstract Authors: Pocernich CB, Bader Lange ML, Sultana R, Butterfield DA Alzheimer's disease (AD) brain is characterized by amyloid β-peptide (Aβ) deposits, neurofibrillary tangles, synapse loss, and extensive oxidative stress. Aβ-induced oxidative stress is indexed by protein oxidation, lipid peroxidation, free radical formation, DNA oxidation and neuronal cell death. Oxidative stress is combated by antioxidants. Antioxidants and nutrition have long been considered as an approach to slow down AD progression. In this review, we focus on antioxidants that have been shown to protect against Aβ-induced oxidative stress, particularly vitamin E, ferulic acid, various polyphenols, including quercetin and resveratrol, α-lipoic acid, N-acetyl-L-cysteine (NAC), curcumin, epigallocatechin gallate (... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878721 Sun, 22 May 2011 23:00:00 +0100 4878721 http://www.medworm.com/index.php?rid=4878719&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605053%26dopt%3DAbstract Authors: Bastianetto S, Krantic S, Chabot JG, Quirion R One of the hallmarks of Alzheimer's disease is the accumulation of senile plaques composed of extra-cellular aggregates of beta-amyloid (Aβ) peptides. It is well established that at least in vitro, Aβ triggers apoptotic cell death via the activation of caspase-dependent and -independent cell death effectors, namely caspase-3 and apoptosis inducing factor (AIF), respectively. Epidemiological studies have reported that elderly people have a lower risk (up to 50%) of developing dementia if they regularly eat fruits and vegetables and drink tea and red wine (in moderation). Numerous studies indicate that polyphenols derived from these foods and beverages account for the observed neuroprotective effects. In particular, we have report... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878719 Sun, 22 May 2011 23:00:00 +0100 4878719 http://www.medworm.com/index.php?rid=4878717&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21605054%26dopt%3DAbstract Authors: Barberger-Gateau P, Samieri C, Féart C, Plourde M Epidemiological studies suggest a protective role of omega-3 poly-unsaturated fatty acids (n-3 PUFA) against Alzheimer's disease (AD). However, most intervention studies of supplementation with n-3 PUFA have yielded disappointing results. One reason for such discordant results may result from inadequate targeting of individuals who might benefit from the supplementation, in particular because of their genetic susceptibility to AD. The ε4 allele of the apolipoprotein E gene (ApoE) is a genetic risk factor for late-onset AD. ApoE plays a key role in the transport of cholesterol and other lipids involved in brain composition and functioning. The action of n-3 PUFA on the aging brain might therefore differ according to ApoE polym... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878717 Sun, 22 May 2011 23:00:00 +0100 4878717 http://www.medworm.com/index.php?rid=4878760&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592047%26dopt%3DAbstract Authors: Pater C While much uncertainty exists in the estimates of the global burden of Alzheimer's disease and about the potential impact of various interventions, there is a widespread acceptance of the fact that the steady increase in the incidence and prevalence of the condition worldwide is becoming a massive public health problem as well as a huge economic burden for all healthcare systems and societies. These heavy demands are further compounded by the poor quality of life of the affected individuals, of their families and of their caregivers. The epidemic proportion of Alzheimer's disease has triggered relentless attempts for development of treatment approaches during the past two decades by a multitude of pharmaceuticals and biotech companies. Commercial development of the ace... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878760 Tue, 17 May 2011 23:00:00 +0100 4878760 http://www.medworm.com/index.php?rid=4878759&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592048%26dopt%3DAbstract Conclusions: No evidence of statistically or clinically significant efficacy in cognition or global function was detected for 2 mg or 8 mg RSG XR as adjunctive therapy to ongoing AChEIs. There was no evidence of an interaction between treatment and APOE status. Safety and tolerability of RSG XR was consistent with the known profile of rosiglitazone. PMID: 21592048 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878759 Tue, 17 May 2011 23:00:00 +0100 4878759 http://www.medworm.com/index.php?rid=4878758&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592049%26dopt%3DAbstract Authors: Horecky J, Gvozdjáková A, Kucharská J, Obrenovich ME, Palacios HH, Li Y, Vančová O, Aliev G It is known that oxidative stress and mitochondrial dysfunction both play an important role in animal models of brain ischemia. The present study was undertaken to test whether oral supplementation of coenzyme Q10 (ubiquinone) or creatine citrate could protect against brain ischemia-induced mitochondrial damage in the rats model. Brain ischemia was induced for 50 minutes with three-vessel occlusion (3-VO). Coenzyme Q10 was administered for 30 days before the ischemic event and coenzyme Q10 or creatine citrate for 30 days post-ischemia. Moreover, the concentrations of coenzyme Q10 and α-, γ- tocopherols as well as the formation of thiobarbituric acid reactive substances (TBARS) we... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878758 Tue, 17 May 2011 23:00:00 +0100 4878758 http://www.medworm.com/index.php?rid=4878757&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592050%26dopt%3DAbstract In this study we aimed to identify the brain regions underlying this deficit. In patients with clinically diagnosed dementia or mild cognitive impairment (MCI) we investigated the relationship between gray matter volume (GMV) and performance on a standardized confrontation naming test. 268 patients with one of three probable etiologies were included: Alzheimer's Dementia (AD), AD with signs of cerebrovascular pathology, and frontotemporal dementia. Applying voxel-based morphometry using a diffeomorphic registration algorithm we contrasted GMV of patients performing within the normal range with those of patients with pathological performance. Further, differential effects of gray matter atrophy on impaired performance in AD versus MCI of AD type were investigated. Results revealed significa... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878757 Tue, 17 May 2011 23:00:00 +0100 4878757 http://www.medworm.com/index.php?rid=4878756&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592051%26dopt%3DAbstract Authors: Rigacci S, Guidotti V, Bucciantini M, Nichino D, Relini A, Berti A, Stefani M Amyloid aggregation starts with the initial misfolding of peptide/protein precursors, with subsequent structural rearrangement into oligomers and protofibrils; the latter eventually organize into fibrils with shared basic structural features, found deposited in amyloid diseases. Mounting evidence indicates early oligomers as the most toxic amyloid species; accordingly, the search of inhibitors of their growth is considered a promising target to prevent amyloid toxicity. We recently showed that oleuropein aglycon, a polyphenol abundant in the extra virgin olive oil, interferes with the aggregation of amylin (involved in type-2 diabetes), eliminating its cytotoxicity. Here we report that oleuropein agl... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878756 Tue, 17 May 2011 23:00:00 +0100 4878756 http://www.medworm.com/index.php?rid=4878755&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592052%26dopt%3DAbstract Authors: Lithner CU, Hedberg MM, Nordberg A During the last few decades, numerous stable transgenic mouse strains have been developed in order to mimic a range of Alzheimer's disease (AD)-related pathologies. Although none of the models fully replicates the human disease, the models have been a key feature in translational research, providing significant insights into the pathophysiology of AD. They have also been widely used in the preclinical testing of potential therapies. The choice of transgenic mouse model, as well as the stage of Aβ pathology, significantly contributes to the outcome of the studies. Therefore, it is important to combine studies in different transgenic mouse models and detailed in vitro experiments to obtain a complete understanding of the origin of the disease,... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878755 Tue, 17 May 2011 23:00:00 +0100 4878755 http://www.medworm.com/index.php?rid=4878754&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592053%26dopt%3DAbstract Authors: Salazar JG, Ribes D, Cabré M, Domingo JL, Sanchez-Santed F, Colomina MT Chlorpyrifos (CPF) is an organophosphate pesticide widely used in intensive agriculture. Various studies have demonstrated delayed neurotoxic effects in adult mammals after acute CPF exposure. This pesticide induces oxidative stress and neuronal damage, which suggests a possible relationship between CPF exposure and Alzheimer's disease (AD). In the present study, we examined in a mice model of AD, long-term changes in the behavior and brain levels of amyloid β after acute CPF exposure. Fifty mg/kg of CPF were subcutaneously injected to Tg2576 (Tg) mice carrying the Swedish amyloid-β protein precursor (AβPP) mutation for AD. General status, body weight, acetyl cholinesterase (AChE) inhibition, and behav... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878754 Tue, 17 May 2011 23:00:00 +0100 4878754 http://www.medworm.com/index.php?rid=4878753&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592054%26dopt%3DAbstract Authors: Ascolani A, Balestrieri E, Minutolo A, Mosti S, Spalletta G, Bramanti P, Mastino A, Caltagirone C, Macchi B Diagnosis and therapeutic strategies in Alzheimer's disease (AD) might greatly benefit of the present multidisciplinary approach for studying the molecular pathogenesis of the disorder. Gene expression profile at peripheral level could be a promising tool for pathogenic studies as well as for early diagnosis of AD. A dysregulated inflammatory response, as well as other systemic disorders, have been described in AD. Therefore, we investigated the expression, at peripheral level, of a number of genes involved in the inflammatory, oxidative stress and proliferative response of a well defined, small cohort of sporadic AD patients. Firstly, the mRNA expression of inflammatory... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878753 Tue, 17 May 2011 23:00:00 +0100 4878753 http://www.medworm.com/index.php?rid=4878752&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592055%26dopt%3DAbstract Authors: Panza F, Frisardi V, Imbimbo BP, Seripa D, Paris F, Santamato A, D'Onofrio G, Logroscino G, Pilotto A, Solfrizzi V Recent advances in our understanding of the neurobiology of Alzheimer's disease (AD) have led to the development of putative disease-modifying treatments. The most revolutionary of these approaches consists in the removal of brain β-amyloid (Aβ) via anti-Aβ antibodies. Brain imaging and neuropathological studies have shown the ability of both active and passive anti-Aβ immunotherapies of clearing Aβ deposits from the brain of the AD patients. An active anti-Aβ vaccine preparation, AN1792, has been used in AD patients with some clues of clinical efficacy but causing meningoencephalitis in about 6% of patients and it has been abandoned. Several second-generati... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878752 Tue, 17 May 2011 23:00:00 +0100 4878752 http://www.medworm.com/index.php?rid=4878751&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592056%26dopt%3DAbstract Conclusions: Odor identification tests combined with neuropsychological tests permit to improve prediction of rapid deterioration of cognitive functions and MCI to dementia conversion. A follow up study of hippocampus volume may further increase prediction accuracy. PMID: 21592056 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878751 Tue, 17 May 2011 23:00:00 +0100 4878751 http://www.medworm.com/index.php?rid=4878750&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592057%26dopt%3DAbstract Authors: Bai F, Watson DR, Shi Y, Yuan Y, Yu H, Zhang Z Brain task-negative networks (default mode network, DMN) and task-positive networks appear to operate largely in opposition, such that task-negative networks show activation during resting states, whilst task-positive networks are deactivated with the reverse being true during goal-oriented behavior. Altered DMN and task-positive network activity has been observed in amnestic mild cognitive impairment (aMCI) subjects. However, no study has directly linked the patterns of between-state differences in the same aMCI cohort regarding these two types of functional networks. The spatial and temporal characteristics of intrinsic, low frequency BOLD signal fluctuations both during resting state and episodic memory fMRI task were assessed ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878750 Tue, 17 May 2011 23:00:00 +0100 4878750 http://www.medworm.com/index.php?rid=4878749&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592058%26dopt%3DAbstract Authors: Miettinen PS, Pihlajamäki M, Jauhiainen AM, Tarkka IM, Gröhn H, Niskanen E, Hänninen T, Vanninen R, Soininen H Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (AChEI) enhances cholinergic activity and alleviates clinical symptoms. In the present functional magnetic resonance imaging (fMRI) study, we investigated the effect of the AChEI rivastigmine on cognitive function and brain activation patterns during a face recognition memory task. Twenty patients with newly-diagnosed mild AD were administered a single oral dose of placebo, a single dose of rivastigmine (acute), and twice-daily treatment with rivastigmine for 4 weeks (chronic). After each treatment, the patients underwent a facial recognition task during fMRI. The prefrontal areas known to b... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4878749 Tue, 17 May 2011 23:00:00 +0100 4878749 http://www.medworm.com/index.php?rid=4826803&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21557719%26dopt%3DAbstract This study examines the ability of tolfenamic acid to reduce SP1 levels, and thereby decrease APP transcription and Aβ levels in rodent brains. Tolfenamic acid was administered by oral gavage to C57BL/6 mice at variable dosages and for different time periods. Results have shown that tolfenamic acid was able to down regulate brain protein levels of SP1, APP, and Aβ. These findings demonstrate that interference with upstream transcriptional pathways can lower pathogenic intermediates associated with AD, and thus tolfenamic acid represents a novel approach for the development of a therapeutic intervention for AD. PMID: 21557719 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4826803 Tue, 10 May 2011 23:00:00 +0100 4826803 http://www.medworm.com/index.php?rid=4826802&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21557720%26dopt%3DAbstract Conclusions: Most experienced raters made at least one error that may affect ADAS-cog scores and clinical trials outcomes. These errors may undermine detection of medication effects by contributing both to a biased point estimate and increased variance of the outcome. PMID: 21557720 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4826802 Tue, 10 May 2011 23:00:00 +0100 4826802 http://www.medworm.com/index.php?rid=4826801&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21557721%26dopt%3DAbstract Authors: Obrien RJ Both Alzheimer's disease type pathology (neuritic plaques and neurofibrillary tangles) and evidence of atherosclerosis and infarcts are common in autopsy specimens from the brains of patients enrolled in longitudinal prospective cohorts; the relative contribution of each of these to overall cognitive function is unclear. In addition whether each of these two forms of brain pathology can accelerate the appearance of the other is also unclear. In this paper we examine the relationship among Alzheimer's brain pathology, cerebral infarcts and cerebral atherosclerosis. We conclude that each is an independent predictor of dementia. Moreover we do not find that atherosclerosis increases Alzheimer's type brain pathology or vice versa. PMID: 21557721 [PubMed - as supplied... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4826801 Tue, 10 May 2011 23:00:00 +0100 4826801 http://www.medworm.com/index.php?rid=4826800&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21557722%26dopt%3DAbstract Authors: Driscoll I, Troncoso J PMID: 21557722 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4826800 Tue, 10 May 2011 23:00:00 +0100 4826800 http://www.medworm.com/index.php?rid=4826806&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21524270%26dopt%3DAbstract Authors: Li A, Zhou C, Moore J, Zhang P, Tsai TH, Lee HC, Romano DM, McKee ML, Schoenfeld DA, Serra MJ, Raygor K, Cantiello HF, Fujimoto JG, Tanzi RE Mutations in the presenilin genes cause the majority of early-onset familial Alzheimer's disease. Recently, presenilin mutations have been identified in patients with dilated cardiomyopathy (DCM), a common cause of heart failure and the most prevalent diagnosis in cardiac transplantation patients. However, the molecular mechanisms, by which presenilin mutations lead to either AD or DCM, are not yet understood. We have employed transgenic Drosophila models and optical coherence tomography imaging technology to analyze cardiac function in live adult Drosophila. Silencing of Drosophila ortholog of presenilins (dPsn) led to significantly redu... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4826806 Tue, 26 Apr 2011 23:00:00 +0100 4826806 http://www.medworm.com/index.php?rid=4826805&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21524271%26dopt%3DAbstract Authors: Kertesz A A significant expansion of knowledge in the last few years, especially in the molecular biology of frontotemporal dementia (FTD) is summarized. This condition, formerly known as Pick's disease and considered rare, is estimated to be 12-15% of all dementias and 30-50% early onset ones. The clinical picture is protean, mainly a behavioural and language impairment, but the extrapyramidal syndromes of CBD and PSP are often seen and conversely FTD and progressive aphasia often has motor symptoms, including ALS. These seemingly different presentations converge, as one or other areas in the brain are affected. Our experience with FTD in a clinical cohort, with high rate of autopsy confirmation is presented. Less than half of the cases are tauopathies, the majority has been ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4826805 Tue, 26 Apr 2011 23:00:00 +0100 4826805 http://www.medworm.com/index.php?rid=4826804&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21524272%26dopt%3DAbstract Authors: Borroni B PMID: 21524272 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4826804 Tue, 26 Apr 2011 23:00:00 +0100 4826804 http://www.medworm.com/index.php?rid=4826807&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470101%26dopt%3DAbstract Authors: Reddy PH, Reddy TP Mitochondria are cytoplasmic organelles responsible for life and death. Extensive evidence from animal models, postmortem brain studies of and clinical studies of aging and neurodegenerative diseases suggests that mitochondrial function is defective in aging and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Several lines of research suggest that mitochondrial abnormalities, including defects in oxidative phosphorylation, increased accumulation of mitochondrial DNA defects, impaired calcium influx, accumulation of mutant proteins in mitochondria, and mitochondrial membrane potential dissipation are important cellular changes in both early and late-onset neurodegenerative ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4826807 Tue, 05 Apr 2011 23:00:00 +0100 4826807 http://www.medworm.com/index.php?rid=4722589&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21453244%26dopt%3DAbstract Authors: Rodríguez JJ, Noristani HN, Olabarria M, Fletcher J, Somerville TD, Yeh CY, Verkhratsky A Alzheimer's disease (AD) affects memory and neurogenesis. Adult neurogenesis plays an important role in memory function and impaired neurogenesis contributes to cognitive deficits associated with AD. Increased physical/cognitive activity is associated with both reduced risk of dementia and increased neurogenesis. Previous attempts to restore hippocampal neurogenesis in transgenic mice by voluntary running (RUN) and environmental enrichment (ENR) provided controversial results due to lack of non-transgenic (non-Tg) control and inclusion of social isolation as "standard" housing environment. Here, we determine the effect of RUN and ENR upon hippocampal neurogenesis in a triple transgenic (... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4722589 Thu, 31 Mar 2011 23:00:00 +0100 4722589 http://www.medworm.com/index.php?rid=4669411&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21453245%26dopt%3DAbstract In this study, we evaluated the effect of chronic psychosocial stress on synaptic plasticity (Late-phase long-term potentiation; L-LTP, and long-term depression; LTD) in the β-Amyloid rat model of AD, and the positive impact of chronic nicotine treatment. Chronic psychosocial stress was induced by an intruder method. The Rat AD model was induced by 14-day i.c.v. osmotic pump infusion of a 1:1 mixture of 300 pmol/day Aβ1-40/Aβ1-42. The rats were treated with nicotine (2 mg/kg/day) for 6 weeks. In vivo electrophysiological recordings of L-LTP, and LTD in hippocampal area CA1 showed that chronic stress by itself did not affect L-LTP. However, it markedly aggravated the impairment of this response as well as LTD in Aβ-treated rats. The effects of Aβ and the combination of stress and Aβ w... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4669411 Thu, 31 Mar 2011 23:00:00 +0100 4669411 http://www.medworm.com/index.php?rid=4669385&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21453246%26dopt%3DAbstract Authors: Alzoubi KH, Alhaider IA, Tran TT, Mosely A, Alkadhi KK Basal synaptic transmission and activity-dependent synaptic plasticity were evaluated in superior cervical sympathetic ganglia (SCG) of amyloid-β rat model of Alzheimer's disease (Aβ rat) using electrophysiological and molecular techniques. Rats were administered Aβ peptides (a mixture of 1:1 Aβ1-40 and Aβ1-42) by chronic intracerebroventricular infusion via 14-day mini-osmotic pumps (300 pmol/day). Control rats received Aβ40-1 (inactive reverse peptide: 300 pmol/day). Ganglionic compound action potentials were recorded before (basal) and after repetitive stimulation. In isolated SCG, ganglionic long-term potentiation (gLTP) was generated by a brief train of stimuli (20Hz for 20s) and ganglionic long-term depression ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4669385 Thu, 31 Mar 2011 23:00:00 +0100 4669385 http://www.medworm.com/index.php?rid=4669337&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21453247%26dopt%3DAbstract Authors: Müller T, Loosse C, Schrötter A, Schnabel A, Helling S, Egensperger R, Marcus K AICD is the intracellular subdomain of the amyloid precursor protein thought to play a pivotal role as a potential transcription factor that might be of relevance for the pathophysiology of Alzheimer's disease. For its signal transduction potential AICD requires interacting proteins like FE65 and TIP60. However, many other proteins were described being able to bind to AICD. Here, we studied mRNA levels of AICD interacting proteins and found one of them (DAB1) strongly up-regulated in human post-mortem frontal cortex brain samples of AD patients. Subsequent cell culture experiments revealed that elevated DAB1 level results in the deregulation of the cellular proteome. We found the proliferation as... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4669337 Thu, 31 Mar 2011 23:00:00 +0100 4669337 http://www.medworm.com/index.php?rid=4722590&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21418002%26dopt%3DAbstract Authors: Naert G, Rivest S Alzheimer disease (AD) is characterized by a progressive cognitive decline and accumulation of β-amyloid (Aβ forming senile plaques that are associated with inflammatory molecules and cells. Resident microglia and newly differentiated cells that are derived from the bone marrow are found in the vicinity of Aβ plaques. Although these two types of microglia are not distinguishable by specific markers in the brain, they seem to possess different phenotype and functions. In mouse models of AD, bone marrow-derived microglia (BMDM) have been shown to delay or stop the progression of AD and preventing their recruitment exacerbates the pathology. Transplantation of competent hematopoietic stem cells or their genetic modifications ameliorate cognitive functions, re... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4722590 Mon, 21 Mar 2011 00:00:00 +0100 4722590 http://www.medworm.com/index.php?rid=4549549&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21348817%26dopt%3DAbstract Curr Alzheimer Res. 2011 Feb 24; Authors: Cuello AC PMID: 21348817 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4549549 Thu, 24 Feb 2011 00:00:00 +0100 4549549 http://www.medworm.com/index.php?rid=4549554&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345166%26dopt%3DAbstract Authors: Rezai-Zadeh K, Gate D, Gowing G, Town T Alzheimer's disease (AD) is pathologically defined by presence of intracellular neurofibrillary tangles and extracellular amyloid plaques comprised of amyoid-β (Aβ) peptides. Despite local recruitment of brain microglia to sites of amyloid deposition, these mononuclear phagocytes ultimately fail at restricting β-amyloid plaque formation. On the other hand, it is becoming increasingly clear that professional phagocytes from the periphery possess Aβ clearance aptitude. Yet, in order to harness this beneficial innate immune response, effective strategies must be developed to coax monocytes/macrophages from the periphery into the brain. It has previously been suggested that Aβ 'immunotherapy' clears cerebral Aβ deposits via mononuclear... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4549554 Wed, 23 Feb 2011 00:00:00 +0100 4549554 http://www.medworm.com/index.php?rid=4549553&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345167%26dopt%3DAbstract Authors: Eikelenboom P, Veerhuis R, Exel EV, Hoozemans JJ, Rozemuller AJ, van Gool WA The idea that an inflammatory process is involved in Alzheimer's disease (AD) was proposed already hundred years ago but only the past twenty years inflammation-related proteins have been identified within plaques. A number of acute-phase proteins colocalize with the extracellular amyloid fibrils, the so called Aβ-associated proteins. Activated microglia and astrocytes surrounding amyloid deposits express receptors of innate immunity and secrete pro-inflammatory cytokines. In this paper we review the evidence for involvement of innate immunity in the early stages of the pathological cascade of AD. Diffuse plaques, the initial neuropathological lesion in the cerebral neocortex, contain next to Aβ als... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4549553 Wed, 23 Feb 2011 00:00:00 +0100 4549553 http://www.medworm.com/index.php?rid=4549552&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345168%26dopt%3DAbstract This article reviews the current knowledge and views on the above mechanisms and critically discusses current obstacles and the potential as future AD therapeutics. PMID: 21345168 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4549552 Wed, 23 Feb 2011 00:00:00 +0100 4549552 http://www.medworm.com/index.php?rid=4549551&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345169%26dopt%3DAbstract Authors: Sastre M, Richardson JC, Gentleman SM, Brooks DJ The importance of inflammatory processes in Alzheimer's disease (AD) progression has been confirmed during the past decade by the intensive investigation of inflammatory mediators in the brain of AD patients as well as by the genetic and drug manipulation of animal models of AD. Imaging studies have revealed that the activation of microglia occurs in early stages of the disease, even before plaque and tangle formation, and is correlated with early cognitive deficits. In this review, we analyze how different risk factors, such as trauma, stroke, infection, and metabolic diseases can lead to an acceleration of the inflammatory response in the AD brain and to an increased risk of developing this disorder. The use of imaging techniq... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4549551 Wed, 23 Feb 2011 00:00:00 +0100 4549551 http://www.medworm.com/index.php?rid=4549550&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345170%26dopt%3DAbstract Authors: Ferretti MT, Cuello AC The occurrence of a plaque-dependent inflammation in Alzheimer's disease has been extensively documented in both human specimens and transgenic models of the disease. Since insoluble plaques are present in AD patients from early preclinical stages of the pathology, the point at which neuroinflammation first occurs in the progression of the AD pathology is still unknown. In this review we discuss the clinical and experimental evidence for the occurrence of inflammation in preclinical, asymptomatic phases of the progression of the AD pathology. In particular, we discuss the evidence from different transgenic models suggesting that a pro-inflammatory process might even be initiated prior to plaque deposition. The factors responsible for the early, pre-plaqu... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4549550 Wed, 23 Feb 2011 00:00:00 +0100 4549550 http://www.medworm.com/index.php?rid=4494904&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21314622%26dopt%3DAbstract Conclusions: These results indicate that examiner-assisted, computerized administration is equivalent to traditional, paper-based administration, and shows significantly greater test-retest reliability. PMID: 21314622 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4494904 Fri, 11 Feb 2011 00:00:00 +0100 4494904 http://www.medworm.com/index.php?rid=4494908&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21294703%26dopt%3DAbstract Authors: Kotwal GJ PMID: 21294703 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4494908 Mon, 07 Feb 2011 00:00:00 +0100 4494908 http://www.medworm.com/index.php?rid=4424684&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21265731%26dopt%3DAbstract Authors: Lahiri DK PMID: 21265731 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424684 Wed, 26 Jan 2011 00:00:00 +0100 4424684 http://www.medworm.com/index.php?rid=4424693&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244348%26dopt%3DAbstract Authors: Coley N, Gardette V, Cantet C, Gillette-Guyonnet S, Nourhashemi F, Vellas B, Andrieu S Missing data are frequent in Alzheimer's disease (AD) trials due to the age of participants and the nature of the disease. This can lead to bias and decreased statistical power. We assessed the level and causes of missing data in a 2-year randomised trial of an AD patient management program (PLASA study), and conducted sensitivity analyses on the primary endpoint (functional decline), using various methods for handling missing data: complete case, LOCF, Z-score LOCF, longitudinal mixed effects model, multiple imputation. By 2 years, 32% of the 1131 subjects had dropped out, with the commonest reasons being death (28% of dropouts) and refusal (22%). Baseline cognitive and functional status we... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424693 Wed, 19 Jan 2011 00:00:00 +0100 4424693 http://www.medworm.com/index.php?rid=4424692&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244349%26dopt%3DAbstract Authors: Xu Z, Dong Y, Wu X, Zhang J, McAuliffe S, Pan C, Zhang Y, Ichinose F, Yue Y, Xie Z β-amyloid protein (Aβ)-induced neurotoxicity is the main component of Alzheimer's disease (AD) neuropathogenesis. Inhalation anesthetics have long been considered to protect against neurotoxicity. However, recent research studies have suggested that the inhalation anesthetic isoflurane may promote neurotoxicity by inducing apoptosis and increasing Aβ levels. We therefore set out to determine whether isoflurane can induce dose- and time-dependent dual effects on Aβ-induced apoptosis: protection versus promotion. H4 human neuroglioma cells, primary neurons from naïve mice, and naïve mice were treated with Aβ and/or isoflurane, and levels of caspase-3 cleavage (activation), apoptosis, Bcl-2,... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424692 Wed, 19 Jan 2011 00:00:00 +0100 4424692 http://www.medworm.com/index.php?rid=4424691&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244350%26dopt%3DAbstract Authors: Scheffler K, Stenzel J, Krohn M, Lange C, Hofrichter J, Schumacher T, Brüning T, Plath AS, Walker L, Pahnke J One early and prominent pathologic feature of Alzheimer's disease (AD) is the appearance of activated microglia in the vicinity of developing β-amyloid deposits. However, the precise role of microglia during the course of AD is still under discussion. Microglia have been reported to degrade and clear β-amyloid, but they also can exert deleterious effects due to overwhelming inflammatory reactions. Here, we demonstrate the occurrence of developing plaque populations with distinct amounts of associated microglia using time-dependent analyses of plaque morphology and the spatial distribution of microglia in an APP/PS1 mouse model. In addition to a population of larger ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424691 Wed, 19 Jan 2011 00:00:00 +0100 4424691 http://www.medworm.com/index.php?rid=4424690&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244351%26dopt%3DAbstract Authors: Brito-Moreira J, Paula-Lima AC, Bomfim TR, Oliveira FB, Sepúlveda FJ, De Mello FG, Aguayo LG, Panizzutti R, Ferreira ST Soluble oligomers of the amyloid-β peptide (AβOs) accumulate in Alzheimer's disease (AD) brain and have been implicated in mechanisms of pathogenesis. The neurotoxicity of AβOs appears to be, at least in part, due to dysregulation of glutamate signaling. Here, we show that AβOs promote extracellular accumulation of glutamate and d-serine, a co-agonist at glutamate receptors of the N-methyl-d-aspartate subtype (NMDARs), in hippocampal neuronal cultures. The increase in extracellular glutamate levels induced by AβOs was blocked by the sodium channel blocker tetrodotoxin (TTX), by the NMDAR blocker (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424690 Wed, 19 Jan 2011 00:00:00 +0100 4424690 http://www.medworm.com/index.php?rid=4424689&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244352%26dopt%3DAbstract Conclusions: The findings indicate that serum TC and LDL levels clearly relate to densities of NP, but not to densities of NFT. The stronger associations found in the subgroup that excluded all subjects with non-AD neuropathology suggest that cerebrovascular involvement does not explain these lipid-plaque relationships. Since the associations of TC/LDL with NP were particularly stronger in ε4 carriers, varying prevalence of this allele may explain some discrepancies among prior studies. PMID: 21244352 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424689 Wed, 19 Jan 2011 00:00:00 +0100 4424689 http://www.medworm.com/index.php?rid=4424688&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244353%26dopt%3DAbstract Authors: Ciro A, Park J, Burkhard G, Yan N, Geula C In Alzheimer's disease, histochemically visualized cholinesterases with altered pH optimum for activity and inhibitable by indoleamines and the protease inhibitor bacitracin emerge in association with plaques and tangles. It has been suggested that these cholinesterases may participate in the pathologic process. However, it is not known whether the properties of cholinesterases observed in Alzheimer's disease are due to requirements of histochemical procedures or actual biochemical properties of these enzymes. Using biochemical assays of acetylcholinesterase and butyrylcholinesterase activities, we demonstrate here that serotonin and bacitracin result in a significantly greater and dose-dependent inhibition of cholinesterases in Alzhe... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424688 Wed, 19 Jan 2011 00:00:00 +0100 4424688 http://www.medworm.com/index.php?rid=4424687&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244354%26dopt%3DAbstract Authors: Ji C, Song C, Zuo P It has been demonstrated that the onset and progression of Alzheimer's disease (AD) are associated with inflammatory disorders in the brain. Although the interactions of inflammatory cytokines with neurotrophins have been reported in vitro, the balance change between inflammatory cytokines and neurotrophic factors (NTFs), such as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF), due to amyloid β (Aβ) chronic administration in vivo is still unclear. The hypothesis of the present study was that the accumulation of Aβ activated glial cells to produce inflammatory mediators and NTFs to maintain the neurons survival, however the failure of crosstalk between NTFs and inflammatory cytoki... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424687 Wed, 19 Jan 2011 00:00:00 +0100 4424687 http://www.medworm.com/index.php?rid=4424686&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244355%26dopt%3DAbstract Authors: Longenberger J, Shah ZA Alzheimer's disease, one of the most common forms of dementia, is a neurodegenerative disorder characterized by progressive cognitive decline and affects as many as 5.3 million people in United States alone. Both Alzheimer's and dementia have tripled the cost of health care for elderly people, amounting to about $148 billion each year. Although there have been numerous drugs designed so far, no ideal or successful drug treatment for Alzheimer's and dementia has been translated into clinical setups. One of the most widely accepted theories of Alzheimer's pathology is the aggregation of amyloid-beta (Aβ) into extracellular cortical and hippocampal plaques. It has also been postulated that excessive cholesterol build-up in the brain plays an integral role... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424686 Wed, 19 Jan 2011 00:00:00 +0100 4424686 http://www.medworm.com/index.php?rid=4424685&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21244356%26dopt%3DAbstract Authors: Diana FF, Silva Esteves AR, Oliveira CR, Cardoso SM Mitochondrial dysfunction has been widely implicated in the etiology of Alzheimer´s disease (AD). Evidence shows a mitochondrial-mediated impairment of autophagy that potentiates amyloid-β (Aβ) deposition. Accordingly, recent data obtained from AD models, in which mitochondrial alterations are a prominent feature, demonstrated abnormalities in microtubule network, involving tubulin and tau post-translational modifications. In this review we will discuss mitochondrial-regulated processes where mitochondrial malfunction is likely to start a sequence of events leading to sirtuin-2 activation, microtubule network breakdown, and impairment of the autophagic pathway. Because sirtuin-2 activity depends on cellular NAD+ availabili... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4424685 Wed, 19 Jan 2011 00:00:00 +0100 4424685 http://www.medworm.com/index.php?rid=4361710&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222590%26dopt%3DAbstract Authors: Yeo RA, Arden R, Jung RE A significant body of evidence has accumulated suggesting that individual variation in intellectual ability, whether assessed directly by intelligence tests or indirectly through proxy measures, is related to risk of developing Alzheimer's disease (AD) in later life. Important questions remain unanswered, however, such as the specificity of risk for AD vs. other forms of dementia, and the specific links between premorbid intelligence and development of the neuropathology characteristic of AD. Lower premorbid intelligence has also emerged as a risk factor for greater mortality across myriad health and mental health diagnoses. Genetic covariance contributes importantly to these associations, and pleiotropic genetic effects may impact diverse organ system... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361710 Tue, 11 Jan 2011 00:00:00 +0100 4361710 http://www.medworm.com/index.php?rid=4361709&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222591%26dopt%3DAbstract Authors: Tucker AM, Stern Y Cognitive reserve explains why those with higher IQ, education, occupational attainment, or participation in leisure activities evidence less severe clinical or cognitive changes in the presence of age-related or Alzheimer's disease pathology. Specifically, the cognitive reserve hypothesis is that individual differences in how tasks are processed provide reserve against brain pathology. Cognitive reserve may allow for more flexible strategy usage, an ability thought to be captured by executive functions tasks. Additionally, cognitive reserve allows individuals greater neural efficiency, greater neural capacity, and the ability for compensation via the recruitment of additional brain regions. Taking cognitive reserve into account may allow for earlier detecti... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361709 Tue, 11 Jan 2011 00:00:00 +0100 4361709 http://www.medworm.com/index.php?rid=4361708&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222592%26dopt%3DAbstract We present data from the Religious Orders Study and the Memory and Aging Project pertaining to pathology and cognition, and propose a paradigm shift in consideration of the neurobiology of healthy aging and dementia. Factors that modify or mediate the association between neuropathology and cognition are also discussed. It is hypothesized that the concept of resilient aging can serve as a useful entity in understanding mechanisms that underlie healthy aging amidst disease-related pathology. PMID: 21222592 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361708 Tue, 11 Jan 2011 00:00:00 +0100 4361708 http://www.medworm.com/index.php?rid=4361707&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222593%26dopt%3DAbstract Authors: Sojkova J, Resnick SM PET imaging agents such as Pittsburgh compound B (PiB) allow detection of fibrillar β-amyloid (Aβ) in vivo. In addition to quantification of Aβ deposition in mild cognitive impairment and Alzheimer's disease, PiB has also increased our understanding of Aβ deposition in older adults without cognitive impairment. In vivo Aβ deposition has been studied in relation to genotype, structural and functional brain changes, as well as alterations in biomarker levels. To date, several studies have reported changes in Aβ burden over time. This, together with investigation of the relationship between Aβ deposition and cognition, sets the stage for elucidation of the temporal sequence of the neurobiological events leading to cognitive decline. Furthermore, corre... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361707 Tue, 11 Jan 2011 00:00:00 +0100 4361707 http://www.medworm.com/index.php?rid=4361706&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222594%26dopt%3DAbstract Authors: Driscoll I, Troncoso J Neuritic plaques and neurofibrillary tangles, the neuropathological hallmarks of AD, are not limited to individuals with dementia. These pathologic changes can also be present in the brains of cognitively normal older adults - a condition we defined as Asymptomatic AD (ASYMAD). Although it remains unclear whether these individuals would remain clinically normal with longer survival, they seem to be able to compensate for or delay the appearance of dementia symptoms. Here, we provide a historical background and highlight the combined clinical, pathologic and morphometric evidence related to ASYMAD. Understanding the nature of changes during this apparently asymptomatic state may shed light on the mechanisms that forestall the progression of the disease an... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361706 Tue, 11 Jan 2011 00:00:00 +0100 4361706 http://www.medworm.com/index.php?rid=4361705&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222595%26dopt%3DAbstract Authors: Beason-Held LL Changes in regional activity levels and network connectivity occur across the lifespan within the default mode network (DMN) of resting brain function. Changes with age are noted in most components of the DMN, especially in medial frontal/anterior cingulate and posterior cingulate/precuneus regions. Individuals with age-related disease such as mild cognitive impairment (MCI) and Alzheimer's disease (AD) demonstrate additional default-related changes particularly in posterior cingulate/precuneus and hippocampal regions. As these regions are areas of known pathologic change in both normal aging and age-related disease, examining DMN activity may allow future studies to more fully assess the relationship between pathology and function in these regions. The ability ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361705 Tue, 11 Jan 2011 00:00:00 +0100 4361705 http://www.medworm.com/index.php?rid=4361704&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222596%26dopt%3DAbstract Authors: Weihl CC Inclusion body myopathy (IBM) associated with paget's disease of the bone (PDB) and fronto-temporal dementia (FTD) or IBMPFD, is a rare multisystem degenerative disorder due to mutations in valosin containing protein (VCP). VCP is a ubiquitously expressed protein that facilitates the degradation of proteins via the ubiquitin proteasome and autophagy pathways. Affected brain and muscle tissue in IBMPFD have ubiquitinated and TAR DNA binding protein-43 (TDP-43) inclusions. In skeletal muscle, this pathology is consistent with IBM. While in the CNS, IBMPFD is a frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) subtype. Recent studies suggest that IBMPFD mutations in VCP disrupt its function in protein degradation. This review will explore the clini... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361704 Tue, 11 Jan 2011 00:00:00 +0100 4361704 http://www.medworm.com/index.php?rid=4361703&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222597%26dopt%3DAbstract Authors: Kaat DL, Chiu WZ, Boon AJ, van Swieten JC Progressive Supranuclear Palsy has been used over decades as a term denoting an uniform disorder with progressive parkinsonism with early falls, vertical supranulcear gaze palsy, pseudobulbar dysfunction and cognitive decline. Over the last decade, heterogeneity of the disease into different clinical subtypes has been recognized in clinicopathological studies. Although neuroimaging features and laboratory findings may support the diagnosis, true biomarkers are still lacking in the clinical setting. Neuronal and glial tau positive aggregates are predominantly found in basal ganglia and brainstem, and the significant association of PSP with the common H1 tau haplotype likely points to a pathophysiological role of the tau protein in the d... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361703 Tue, 11 Jan 2011 00:00:00 +0100 4361703 http://www.medworm.com/index.php?rid=4361702&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222598%26dopt%3DAbstract Authors: Rohrer JD, Schott JM The primary progressive aphasias (PPA) are a group of clinically, genetically and pathologically heterogeneous neurodegenerative disorders caused by FTLD-tau, FTLD-TDP or Alzheimer's disease pathology. Clinically, three subtypes are recognized, the semantic, logopenic and nonfluent variants but there remains ongoing discussions over how the clinical subtypes should be dissected. This review looks at the genetic and pathological basis of PPA and argues that with the advent of clinical trials in PPA, establishing the underlying pathology accurately during life will become increasingly important. Current and future biomarkers that may help make a pathological diagnosis in life, i.e. PPA-tau, PPA-TDP and PPA-AD, are reviewed including clinical and neuropsychol... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361702 Tue, 11 Jan 2011 00:00:00 +0100 4361702 http://www.medworm.com/index.php?rid=4361701&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222599%26dopt%3DAbstract Authors: Isaacs AM, Johannsen P, Holm I, Nielsen JE, CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient. These mutations lead to C-terminal truncations of the CHMP2B protein and we will review recent advances in our understanding of the molecular effects of these mutant truncated proteins on vesicular fusion events within the endosome-lysosome and autophagy degradation pathways. We will also review the clinical features of FTD caused by CHMP2B truncation mutations as well as new brain imaging and neuropathological findings. Finally, we collate ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361701 Tue, 11 Jan 2011 00:00:00 +0100 4361701 http://www.medworm.com/index.php?rid=4361700&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222600%26dopt%3DAbstract Authors: Ferrari R, Kapogiannis D, Huey ED, Momeni P The first reports of disorders that in terms of cognitive and behavioral symptoms resemble frontotemporal dementia (FTD) and in terms of motor symptoms resemble amyotrophic lateral sclerosis (ALS) bring us back to the second half of the 1800s. Over the last 150 years, and especially in the last two decades, there has been growing evidence that FTD signs can be seen in patients primarily diagnosed with ALS, implying clinical overlap among these two disorders. In the last decade pathological investigations and genetic screening have contributed tremendously in elucidating the pathology and genetic variability associated with FTD and ALS. To the most important recentdiscoveries belong TAR DNA binding protein [TARDBP or TDP-43] and the f... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361700 Tue, 11 Jan 2011 00:00:00 +0100 4361700 http://www.medworm.com/index.php?rid=4361699&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222601%26dopt%3DAbstract Authors: Davies RR, Kipps CM We review the practical importance of lobar atrophy in frontotemporal dementia (FTD), for diagnosis and prognosis. We discuss specific patterns of frontotemporal atrophy that denote clinical and pathological subtypes of FTD (e.g. semantic dementia). We also discuss the unsatisfactory clinical experience of interpreting MRI scans in individual FTD cases, especially the behavioural presentations (without aphasic or motor impairments). This issue is explored by examining the FTD phenocopy concept. Lobar atrophy emerges as a key observation in defining behavioural FTD patients whose symptoms are likely to progress. In a situation where objective clinical data are few, we highlight the importance of applying caution before diagnosing FTD is the absence of visibl... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361699 Tue, 11 Jan 2011 00:00:00 +0100 4361699 http://www.medworm.com/index.php?rid=4361698&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222602%26dopt%3DAbstract Authors: Budini M, Baralle FE, Buratti E Two proteins have recently received considerable attention in the neurodegenerative research field: TDP-43 and FUS/TLS. The reason is that both proteins have been found to represent major protein components of the intracellular inclusions occurring in the neuronal tissues of patients affected by Fronto Temporal Lobar Degeneration and Amyotrophic Lateral Sclerosis. One of the most interesting features of this discovery is that both proteins have in common several structural properties. In particular, they are multifunctional RNA-binding proteins (RBPs) already known to play a role in several cellular processes such as transcription, pre-mRNA splicing, and mRNA stability. The potential consequences of changes in their intracellular localization an... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361698 Tue, 11 Jan 2011 00:00:00 +0100 4361698 http://www.medworm.com/index.php?rid=4361697&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222603%26dopt%3DAbstract Authors: Alberici A, Cosseddu M, Padovani A, Borroni B Frontotemporal Lobar degeneration (FTLD) is one of the most important neurodegenerative conditions, affecting in the presenium, but more recently recognized also in aged population. The strong genetic background, along with autopsy determinations prompted the identification of the two major genes associated to the disease: MAPT gene, and Progranulin (PGRN) gene. In this review, we highlighted the milestones of these discoveries, and their implication for the development of future therapeuthical approaches. PMID: 21222603 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361697 Tue, 11 Jan 2011 00:00:00 +0100 4361697 http://www.medworm.com/index.php?rid=4361696&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222604%26dopt%3DAbstract Conclusions: These first encouraging safety results do support further development of EHT0202 in order to assess its clinical efficacy and to confirm its tolerability in a larger cohort of Alzheimer patients and for a longer period. PMID: 21222604 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361696 Tue, 11 Jan 2011 00:00:00 +0100 4361696 http://www.medworm.com/index.php?rid=4361695&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222605%26dopt%3DAbstract Authors: Williamson R, Sutherland C Membrane rafts are sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts isolated from post-mortem AD brain are enriched in both β-amyloid and phosphorylated tau. Proteolytic processing of APP to generate β-amyloid, the principle component of amyloid plaques, can occur in membrane rafts, implicating them in the pathogenesis of Alzheimer's disease (AD). Secondary to their role in β-amyloid generation, membrane rafts have more recently been implicated in the accumulation, aggregation and degradation of β-amyloid, with evidence supporting a specific role for membrane raft gangliosides in the binding and aggregation of β-amyloid. In addition, membrane domain composition has a direct impact on both the gen... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361695 Tue, 11 Jan 2011 00:00:00 +0100 4361695 http://www.medworm.com/index.php?rid=4361694&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222606%26dopt%3DAbstract The objective of this study was to elucidate an association between Apo- Eε4 allele and CSF biomarkers Aβ42 and tau for the diagnosis of Alzheimer's Disease (AD) patients. Aβ42 and tau protein concentrations in CSF were measured by using ELISA assays. The levels of Aβ42 were found to be decreased where as tau levels increased in AD patients. Moreover in AD patients Apo-Eε4 allele carriers have shown low Aβ42 levels (328.86 ± 99.0 pg/ml) compared to Apo-Eε4 allele non-carriers (367.52 ± 5 7.37 pg/ml), while tau levels were higher in Apo-Eε4 allele carriers (511 ± 44.67 pg/ml) compared to Apo-Eε4 allele non-carriers (503.75 ± 41.08 pg/ml). Combination of Aβ42 and tau resulted in sensitivity of 75.38% and specificity of 94.82% and diagnostic accuracy of 84.30% for AD compared wi... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361694 Tue, 11 Jan 2011 00:00:00 +0100 4361694 http://www.medworm.com/index.php?rid=4361693&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21222607%26dopt%3DAbstract Conclusions: Patients who demonstrate improvement, stability, or limited cognitive decline 2-5 months after reaching maintenance doses of galantamine are more likely to experience continued benefit from long-term galantamine therapy. PMID: 21222607 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4361693 Tue, 11 Jan 2011 00:00:00 +0100 4361693 http://www.medworm.com/index.php?rid=4261644&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143154%26dopt%3DAbstract Authors: Veerhuis R In Alzheimers's disease (AD) a disturbed balance between synthesis and removal of Aβ leads to the formation of Aβ deposits and a reaction of the innate immune system. Little evidence exists for a contribution of the adaptive immune response in AD, as no signs of influx of blood borne cells or presence of immunoglobulins in Aβ deposits are apparent. Factors of the complement(C) system and pentraxins act as pattern recognition molecules and mediate uptake of Aβ by glial cells expressing C-receptors (Crec). These interactions may, however, also lead to synthesis and secretion of reactive oxygen species (ROS), cytokines, chemokines and other potentially neurotoxic agents by the glial cells. Virtually all complement factors are produced in brain, and the expression i... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4261644 Tue, 14 Dec 2010 00:00:00 +0100 4261644 http://www.medworm.com/index.php?rid=4261628&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143155%26dopt%3DAbstract Authors: Viel TA, Buck HS The kallikrein-kinin system (KKS) has been associated to inflammatory and immunogenic responses in the peripheral and central nervous system by the activation of two receptors, namely B1 receptor and B2 receptor. The B1 receptor is absent or under-expressed in physiological conditions, being up-regulated during tissue injury or in the presence of cytokines. The B2 receptor is constitutive and mediates most of the biological effects of kinins. Some authors suggest a link between the KKS and the neuroinflammation in Alzheimer's disease (AD). We have recently described an increase in bradykinin (BK) in the cerebrospinal fluid and in densities of B1 and B2 receptors in brain areas related to memory, after chronic infusion of amyloid-beta (Aβ) peptide in rats, whi... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4261628 Tue, 14 Dec 2010 00:00:00 +0100 4261628 http://www.medworm.com/index.php?rid=4261559&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143156%26dopt%3DAbstract Authors: Gonzalez-Velasquez FJ, Reed JW, Fuseler JW, Matherly EE, Kotarek JA, Soto-Ortega DD, Moss MA Cerebrovascular accumulation of amyloid-β protein (Aβ) aggregates in Alzheimer's disease (AD) is proposed to contribute to disease progression and brain inflammation as a result of Aβ-induced increases in endothelial monolayer permeability and stimulation of the endothelium for cellular adhesion and transmigration. These deficiencies facilitate the entry of serum proteins and monocyte-derived microglia into the brain. In the current study, a role for nuclear factor-κB (NF-κB) in the activation of cerebral microvascular endothelial cells by Aβ is explored.Quantitative immunocytochemistry is employed to demonstrate that Aβ(1-40) preparations containing isolated soluble aggregates ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4261559 Tue, 14 Dec 2010 00:00:00 +0100 4261559 http://www.medworm.com/index.php?rid=4261529&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143157%26dopt%3DAbstract Authors: Kulkarni AP, Govender DA, Kotwal GJ, Kellaway LA Widespread neuroinflammation in the central nervous system (CNS) of Alzheimer's disease (AD) patients, involving pro-inflammatory mediators such as complement components, might be responsible for AD associated behavioral symptoms such as anxiety. Vaccinia virus complement control protein (VCP) and curcumin (Cur) are the bioactive compounds of natural origin shown to inhibit the in-vitro complement activation. In order to develop complement regulatory compounds which could be delivered to the CNS by a non-invasive route, VCP, its truncated version (tVCP), and Cur were administered to Wistar rats intranasally. The distribution of these compounds in cerebrospinal fluid (CSF) was studied using an enzyme linked immunosorbent assay (E... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4261529 Tue, 14 Dec 2010 00:00:00 +0100 4261529 http://www.medworm.com/index.php?rid=4261520&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143158%26dopt%3DAbstract Authors: Li C, Zhao R, Gao K, Wei Z, Yin MY, Lau LT, Chui D, Yu AC Alzheimer's disease (AD) is a neurodegenerative disease with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Neuroinflammation is involved in the onset of several neurodegenerative disorders. Astrocyte is the most abundant type of glial cells in the central nervous system (CNS) and appears to be involved in the induction of neuroinflammation. Under stress and injury, astrocytes become astrogliotic leading to an upregulation of the expression of proinflammatory cytokines and chemokines, which are associated with the pathogenesis of AD. Cytokines and related molecules play roles in both neuroprotection and neurodegeneration in the CNS. During early AD pathogenesis, amyloid beta (Aβ), S100B an... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4261520 Tue, 14 Dec 2010 00:00:00 +0100 4261520 http://www.medworm.com/index.php?rid=4261511&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143159%26dopt%3DAbstract Authors: Ferretti MT, Partridge V, Leon WC, Canneva F, Allard S, Arvanitis DN, Vercauteren F, Houle D, Ducatenzeiler A, Klein WL, Glabe CG, Szyf M, Cuello AC At diagnosis, Alzheimer's disease (AD) brains are extensively burdened with plaques and tangles and display a degree of synaptic failure most likely beyond therapeutic treatment. It is therefore crucial to identify early pathological events in the progression of the disease. While it is not currently feasible to identify and study early, pre-clinical stages of AD, transgenic (Tg) models offer a valuable tool in this regard. Here we investigated cognitive, structural and biochemical CNS alterations occurring in our newly developed McGill-Thyl-APP Tg mice (over-expressing the human amyloid precursor protein with the Swedish and Indi... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4261511 Tue, 14 Dec 2010 00:00:00 +0100 4261511 http://www.medworm.com/index.php?rid=4261507&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143177%26dopt%3DAbstract In this study we investigated superior temporal and occipital cortical sections from ten AD and ten control group brains (CG). They were examined using immunohistochemical techniques staining for β(42) amyloid, APOE, VEGF and eNOS. The densities of senile plaques (SPs) and APOE, VEGF and eNOS positive capillaries in each region and in each AD and CG condition were compared using nonparametric statistical analysis. In the AD cases, there were significant negative correlations between APOE positive capillaries and β(42) amyloid SPs, and positive correlations between APOE positive capillaries and VEGF and eNOS positive capillaries. These results demonstrate the increased presence of APOE activity in AD brain capillaries, and that there is a positive correlation between the expression of APO... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4261507 Tue, 14 Dec 2010 00:00:00 +0100 4261507 http://www.medworm.com/index.php?rid=4115483&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20977411%26dopt%3DAbstract Authors: Hatip BF, Hatip-Al-Khatib I, Matsunaga Y, Suenaga M, Sen N Amyloid-protein (Aβ) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's disease. Blocking this process could have a therapeutic value. β-sheet breaker peptides (βSBP) decrease Aβfibrillogenesis and neurotoxicity by preventing or dissolving misfolded Aβaggregates. The present study investigated the effects of βSBPs on Aβ40-related neuropathology, memory impairment in 8-armed radial maze and expression of Aβ40 in brain and serum. Aβ40 was injected into amygdaloid nucleus followed 8 days later by octapeptideβSBPs 15-22, 16-23 and 17-24. Aβ40 was detected not only in amygdala, but also in serum. Aβ40 induced cellular changes in amygdala... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4115483 Mon, 25 Oct 2010 23:00:00 +0100 4115483 http://www.medworm.com/index.php?rid=4099099&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20964623%26dopt%3DAbstract In this study, we demonstrated that IL-3 significantly reduced Aβ-promoted neurite degeneration and toxicity. Thus, this cytokine provides cellular protection against Aβ neurotoxicity in primary cortical neuronal cells, by modulating microtubular dynamics and prevention of tau cleavage and hyperphosphorylation. We also demonstrates that IL-3 is expressed in the "in vivo" mouse model of AD, Tg2576, which also expresses human AβPP with the Swedish mutation. In summary, these results suggest that IL-3 could play a neuroprotective role in AD. PMID: 20964623 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=4099099 Thu, 21 Oct 2010 23:00:00 +0100 4099099 http://www.medworm.com/index.php?rid=3867234&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20704554%26dopt%3DAbstract Authors: Vandrovcova J, Anaya F, Kay V, Lees A, Hardy J, de Silva R Fibrillar aggregates of abnormally hyperphosphorylated tau protein are the major component of the pathological entities, including intraneuronal neurofibrillary tangles that define the broad class of late-onset neurodegenerative disorders called the tauopathies. Mutations in the tau gene (MAPT) causing familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) confirm that tau protein dysfunction could be a primary cause of neuronal loss. However, in the sporadic tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) where MAPT mutation is absent, common variation in MAPT that defines the H1 and H2 haplotype clades strongly influences disease risk. Surpris... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3867234 Sun, 01 Aug 2010 23:00:00 +0100 3867234 http://www.medworm.com/index.php?rid=3867233&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20704555%26dopt%3DAbstract Authors: Fioravanzoa L, Venturinib M, Di Liddob R, Marchia F, Grandib C, Parnigottob PP, Folina M Evidence has suggested that it is also a vascular pathology characterized by increased capillary density and expression of angiogenic factors. In AD the endothelium degenerates, promoting local neuroinflammation and activation of brain endothelium, perivascular microglia, pericytes, astrocytes. Excess tumor necrosis factor (TNF) in the cerebrospinal fluid (CSF), at a concentration of 25 times higher than in the control group, has been demonstrated in AD. Recent studies provide evidence that treatment with TNF-alpha antagonists may result in a rapid cognitive improvement in AD patients. In the present work we investigated the role of astrocytes in AD angiogenesis and neuroinflammation by me... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3867233 Sun, 01 Aug 2010 23:00:00 +0100 3867233 http://www.medworm.com/index.php?rid=3867232&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20704556%26dopt%3DAbstract Authors: Jantaratnotai N, Schwab C, Ryu JK, McGeer PL, McLarnon JG We have investigated physical properties of microvasculature and vessel association with microglial clusters in cortical tissue from Alzheimer disease individuals, classified as severe (ADsev) or mild (ADmild), and nondemented controls (ND). Immunostaining with laminin or von Willerbrand factor demonstrated numbers of microvessels and microvascular density were significantly higher in ADsev cases compared with levels in ADmild or ND cases suggesting proangiogenic activity in ADsev brain. Evidence for extravascular laminin immunoreactivity was found in ADsev tissue and was largely absent in ADmild and ND cases suggesting vascular remodeling in ADsev brain included abnormalities in blood vessels. Microgliosis was progress... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3867232 Sun, 01 Aug 2010 23:00:00 +0100 3867232 http://www.medworm.com/index.php?rid=3867231&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20704557%26dopt%3DAbstract Authors: Kobak KA The increasing rate of failed trails found in mood and anxiety disorders is now being seen in Alzheimer's studies. Factors related to the administration of clinician rating scales, such as poor inter-rater reliability, poor interview quality and rater bias may be a contributing factor. Studies have found inter-rater reliability to be problematic in Alzheimer's studies, even with less subjective outcome measures. Lack of standardization of administration and scoring procedures has been identified as a major contributing factor. Remediation through better training procedures has been found to be successful, although ongoing calibration is needed to prevent rater drift. Expectancy bias and baseline score inflation is more difficult to remediate. Inflation of baseline sco... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3867231 Sun, 01 Aug 2010 23:00:00 +0100 3867231 http://www.medworm.com/index.php?rid=3867230&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20704558%26dopt%3DAbstract Authors: Pflanzner T, Kuhlmann CR, Pietrzik CU Alzheimer's disease (AD) is the most common form of dementia in the elderly with more than 26 million people worldwide living with the disease. Besides the main neuropathological hallmarks of AD, provoked by the accumulation of amyloid-beta (Abeta) and tau hyperphosphorylation, other cells and cellular systems such as microglia and the neurovascular unit establishing the blood-brain-barrier (BBB) have been implicated to play a role in AD etiopathology. Insulating the brain from the blood stream, the BBB facilitates supply and disposal of nutrients and metabolites by the expression of transporters and transcytotic receptors at the polarized endothelial cell (EC) surface. Recently, several proteins involved in Abeta transport across the BBB ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3867230 Sun, 01 Aug 2010 23:00:00 +0100 3867230 http://www.medworm.com/index.php?rid=3867229&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20704559%26dopt%3DAbstract Authors: Marra C, Ferraccioli M, Vita MG, Quaranta D, Gainotti G According to recent criteria, Mild Cognitive Impairment (MCI) represents a clinical condition with multiple cognitive presentations (amnesic and non amnesic) that can be supported by different types of brain lesions (mainly vascular and atrophic). In order to asses if the cognitive presentation and the rate of progression differ according to the type of brain pathology, two populations of MCI patients, characterized by hippocampal atrophy (n: 39) and vascular subcortical pathology (n: 36) respectively, on the basis of MRI findings, were investigated. Patients underwent an extensive neuropsychological test battery twice (at baseline and at two years follow-up), which is made up of the MMSE and various tests of episodic mem... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3867229 Sun, 01 Aug 2010 23:00:00 +0100 3867229 http://www.medworm.com/index.php?rid=3867228&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20704560%26dopt%3DAbstract Authors: Becker RE, Greig NH Recent studies of Alzheimer's disease (AD) and other neuropsychiatric drug developments raise questions whether failures of some drugs occur due to flaws in methods. In three case studies of recent AD drug development failures with phenserine, metrifonate, and tarenflurbil we identified methodological lapses able to account for the failures. Errors in complex systems such as drug developments are both almost inescapable due to human mistakes and most frequently hidden at the time of occurrence and thereafter. We propose preemptive error management as a preventive strategy to exclude or control error intrusions into neuropsychiatric drug developments. We illustrate the functions we anticipate for a preemptive error management preventive strategy with a check... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3867228 Sun, 01 Aug 2010 23:00:00 +0100 3867228 http://www.medworm.com/index.php?rid=3867227&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20704561%26dopt%3DAbstract This report identifies ABCA2 as a key regulator of endogenous APP expression and processing and suggests a possible biochemical mechanism linking ABCA2 expression, APP processing and Alzheimer's disease. PMID: 20704561 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3867227 Sun, 01 Aug 2010 23:00:00 +0100 3867227 http://www.medworm.com/index.php?rid=3828352&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20678067%26dopt%3DAbstract Authors: Whittington RA, Papon MA, Chouinard F, Planel E Alzheimer's disease (AD) remains a major health problem, and accounts for 50 to 60% of all cases of dementia. The two histopathological hallmarks of AD are senile plaques, composed of the beta-amyloid peptide (Abeta), and intraneuronal neurofibrillary tangles composed of abnormally hyperphosphorylated tau protein. Only a small proportion of AD is due to mutations in the genome of patients, the large majority of cases being of late onset and sporadic in origin. The relative contribution of genetics and environment to the sporadic cases is unclear, but they are accepted to be of multifactorial origin. This means that genetic and environmental factors can interact together to induce or accelerate the disease. Among environmental fac... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3828352 Sun, 01 Aug 2010 23:00:00 +0100 3828352 http://www.medworm.com/index.php?rid=3828351&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20678068%26dopt%3DAbstract Authors: Hernández F, Avila J Tau is a sticky protein mainly expressed by neurons, which may be found in different subcellular fractions or outside the cell. Tau is mainly associated to microtubules in the cytoplasm, although besides tubulin, tau can also bind to other proteins and to itself to form different polymers, some of which are relevant in pathological disorders. In this short review, we have revised some of the interactions involving tau, both inside or outside of the cell. Different regions of tau are involved in these interactions and some of them are more conserved throughout evolution than others. PMID: 20678068 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3828351 Sun, 01 Aug 2010 23:00:00 +0100 3828351 http://www.medworm.com/index.php?rid=3828350&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20678069%26dopt%3DAbstract Authors: Gozes I The current review discusses microtubules and tau in the healthy brain and move on to the underling pathology of Alzheimer's disease (AD) with emphasis on tau and neurofibrillary tangles. Tangles have been associated with cognitive dysfunction causing neurodegeneration in the absence of plaques. AD, the most abundant tauopathy is characterized by beta-amyloid plaques and tau tangles. An abundance of tau inclusions, in the absence of beta-amyloid deposits, defines Pick's disease (frontotemporal lobar degeneration), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases. Our own focused research is on activity-dependent neuroprtective protein (ADNP). Our findings show that ADNP-deficiency leads to tauopathy which is inhibited by the ADNP... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3828350 Sun, 01 Aug 2010 23:00:00 +0100 3828350 http://www.medworm.com/index.php?rid=3828349&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20678070%26dopt%3DAbstract Authors: Takashima A Based on the amyloid hypothesis, studies for AD therapy have been mostly focused on removing beta-amyloid. Recent results of amyloid immunotherapy raised the question whether beta-amyloid is sufficient target for AD therapy. Neurofibrillary tangles (NFTs), which contain hyperphosphorylated tau, are another pathological hallmark of AD. NFTs are observed in entorhinal cortex, limbic, and neocortex over the course of clinical progression. NFTs are associated with synapse and neuron loss, suggesting that the process of NFT formation is involved in brain dysfunction. During NFT formation, tau forms a variety of different aggregation species, including tau oligomers, granules, and fibrils. Analysis of different human tau-expressing mouse lines reveals that soluble hyperp... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3828349 Sun, 01 Aug 2010 23:00:00 +0100 3828349 http://www.medworm.com/index.php?rid=3828348&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20678071%26dopt%3DAbstract Authors: Kovacech B, Novak M Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer's disease (AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD, most notably hyperphosphorylation and truncation. Hyperphosphorylation is widely regarded as the hottest candidate for the inducer of the neurofibrillary pathology. However, the true nature of the impetus that initiates the whole process in the human brains remains unknown. In AD, several site-specific tau cleavages were identified and became connected to the progression of the disease. In addition, western blot ana... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3828348 Sun, 01 Aug 2010 23:00:00 +0100 3828348 http://www.medworm.com/index.php?rid=3828347&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20678072%26dopt%3DAbstract Authors: Deture M, Hicks C, Petrucelli L Heat shock proteins are members of a large family that function normally in nascent protein folding and the removal of damaged proteins and are able to respond to cellular stresses such as thermal insult to prevent catastrophic protein aggregation. A number of the most common neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are characterized by such abnormal protein folding and aggregation, and the induction of the heat shock response is observed in these cases through their increased expression and often localization within the inclusions. Tau proteins form the major structural component of the neurofibrillary protein aggregates that correlate with cognitive decline in Alzheimer's disease, and appropriately this abnormal... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3828347 Sun, 01 Aug 2010 23:00:00 +0100 3828347 http://www.medworm.com/index.php?rid=3828346&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20678073%26dopt%3DAbstract Authors: Souter S, Lee G Microtubule-associated protein tau has long been known for its ability to promote microtubule assembly. A less known feature of tau is its existence as a non-microtubule associated protein. Here we review the interactions of tau with other proteins, some of which interact with the microtubule binding repeat region of tau. The tau interactions with Fyn and with Pin1 have attracted the most attention and both interactions have been thought to have a role in Alzheimer's disease. The fact that tau has unknown cellular functions is further evidenced by its involvement in cell cycle activated neurodegeneration. One possible route for additional investigations stems from the presence of tau in non-neuronal cells where its characteristics have been largely unknown, alt... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3828346 Sun, 01 Aug 2010 23:00:00 +0100 3828346 http://www.medworm.com/index.php?rid=3828345&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20678074%26dopt%3DAbstract Authors: Iqbal K, Liu F, Gong CX, Grundke-Iqbal I Tau is the major microtubule associated protein (MAP) of a mature neuron. The other two neuronal MAPs are MAP1 and MAP2. An established function of MAPs is their interaction with tubulin and promotion of its assembly into microtubules and stabilization of the microtubule network. The microtubule assembly promoting activity of tau, a phosphoprotein, is regulated by its degree of phosphorylation. Normal adult human brain tau contains 2-3 moles phosphate/mole of tau protein. Hyperphosphorylation of tau depresses this biological activity of tau. In Alzheimer disease (AD) brain tau is ~three to four-fold more hyperphosphorylated than the normal adult brain tau and in this hyperphosphorylated state it is polymerized into paired helical filame... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3828345 Sun, 01 Aug 2010 23:00:00 +0100 3828345 http://www.medworm.com/index.php?rid=3763121&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20626335%26dopt%3DAbstract Authors: Fitzgerald PJ Loss of norepinephrine (NE) releasing neurons, in the locus coeruleus of the brainstem, is well documented to occur in Alzheimer's disease (AD). However, this process does not necessarily result in decreased release of NE, since compensatory mechanisms may produce increased release of this neurotransmitter. Independent of potential loss of locus coeruleus cells, brain NE levels may be elevated in some persons with AD, both before and during disease progression. Here I examine evidence that elevated, endogenous brain NE is an etiological factor in some cases of AD, and not merely an epiphenomenon of the disease. To explore this etiological hypothesis in AD, I examine the following eight lines of evidence: 1) direct evidence of elevated NE or its metabolites in AD;... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3763121 Tue, 13 Jul 2010 23:00:00 +0100 3763121 http://www.medworm.com/index.php?rid=3559051&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455859%26dopt%3DAbstract Conclusions: Low HDL is strongly associated with adverse coronary and cerebrovascular outcomes. Our results indicate that low HDL levels are also associated with more severe WMC lesions on MRI. Dietary or medical adjustment of HDL levels could have important implications for treatment and prevention of cerebral WMC, cerebrovascular and neurodegenerative diseases such as stroke and dementia. PMID: 20455859 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559051 Mon, 10 May 2010 23:00:00 +0100 3559051 http://www.medworm.com/index.php?rid=3559050&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455860%26dopt%3DAbstract Authors: Valotassiou V, Archimandritis S, Sifakis N, Papatriantafyllou J, Georgoulias P The definite diagnosis of Alzheimer's disease (AD) is based on the detection of beta amyloid (Abeta) plaques and neurofibrillary tangles (NFTs) - which are the pathological hallmarks of the disease- in the postmortem brains. Although regional Cerebral Blood Flow (rCBF) and Cerebral Glucose Metabolism (CGM) abnormalities have already been studied in AD patients with Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET), the development of specific imaging agents for direct mapping of Abeta plaques in the living brain, is a great challenge. Abeta probes could significantly contribute to the early diagnosis of AD, the elucidation of the underlying neuropathological p... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559050 Mon, 10 May 2010 23:00:00 +0100 3559050 http://www.medworm.com/index.php?rid=3559049&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455861%26dopt%3DAbstract Conclusions: tHcy is an independent risk factor for developing moderate to severe DWMHs in AD but shows non-significant effect on cognitive performance. The close association between high WMH score and poor initial MMSE suggests an additive impact in AD. The long-term effect of elevated tHcy on cognitive decline was not conclusive in the two-year follow-up period. PMID: 20455861 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559049 Mon, 10 May 2010 23:00:00 +0100 3559049 http://www.medworm.com/index.php?rid=3559048&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455862%26dopt%3DAbstract Conclusions: NPS were more prevalent in AD and MCI patients than in controls. In AD and MCI patients apathy and depression were the most prevalent NPS. The prevalence and the mean scores of all symptoms gradually increased along the severity of the disease, except for sleep and appetite disorders. We have no found a relationship between neuropsycological test and the presence of NPS, but in patients with mild and moderate-severe AD there is a relationship with daily living scales. PMID: 20455862 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559048 Mon, 10 May 2010 23:00:00 +0100 3559048 http://www.medworm.com/index.php?rid=3559047&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455863%26dopt%3DAbstract Conclusions: Although neither apoE plasma levels, nor apoE polymorphism in patients presenting with mild/moderate or severe atheromatosis showed to be associated with CAD severity, the presence of atheromatosis in the heart vessels positively correlated with cognitive dysfunction. PMID: 20455863 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559047 Mon, 10 May 2010 23:00:00 +0100 3559047 http://www.medworm.com/index.php?rid=3559046&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455864%26dopt%3DAbstract Authors: Ullrich C, Mlekusch R, Kuschnig A, Marksteiner J, Humpel C Alzheimer's disease (AD) is a severe chronic neurodegenerative disease. During aging and neurodegeneration, misfolded proteins accumulate and activate the ubiquitin-proteasome system. The aim of the present study is to explore whether ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, ubiquitin or proteasome activity are affected in peripheral blood mononuclear cells (PBMC) of AD, mild cognitive impairment (MCI) and Parkinson's disease (PD) patients compared to healthy subjects. PBMCs were isolated from EDTA blood samples and extracts were analyzed by Western Blot. Proteasome activity was measured with fluorogenic substrates. When compared to healthy subjects, the concentration of enzyme E1 was increased ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559046 Mon, 10 May 2010 23:00:00 +0100 3559046 http://www.medworm.com/index.php?rid=3559045&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455865%26dopt%3DAbstract Authors: Dauwels J, Vialatte F, Cichocki A This paper reviews recent progress in the diagnosis of Alzheimer's disease (AD) from electroencephalograms (EEG). Three major effects of AD on EEG have been observed: slowing of the EEG, reduced complexity of the EEG signals, and perturbations in EEG synchrony. In recent years, a variety of sophisticated computational approaches has been proposed to detect those subtle perturbations in the EEG of AD patients. The paper fi rst describes methods that try to detect slowing of the EEG. Next the paper deals with several measures for EEG complexity, and explains how those measures have been used to study fl uctuations in EEG complexity in AD patients. Then various measures of EEG synchrony are considered in the context of AD diagnosis. Also the issu... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559045 Mon, 10 May 2010 23:00:00 +0100 3559045 http://www.medworm.com/index.php?rid=3559044&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455866%26dopt%3DAbstract Authors: Lee JK, Jin HK, Bae JS Amyloid beta (Abeta) peptide plays a central role in neuronal apoptosis, promoting oxidative stress, lipid peroxidation, caspase pathway activation and neuronal loss. Our previous study has shown that bone marrow-derived mesenchymal stem cells (BM-MSCs) reduce Abeta deposition when transplanted into acutely-induced Alzheimer's disease (AD) mice brain. However, the impact of reduced Abeta deposition on memory impairment and apoptosis by BM-MSCs has not yet been investigated. Therefore, the aim of the present study was to investigate the neuroprotective mechanism of BM-MSCs in vitro and in vivo. We found that BM-MSCs attenuated Abeta-induced apoptotic cell death in primary cultured hippocampal neurons by activation of the cell survival signaling pathway. T... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559044 Mon, 10 May 2010 23:00:00 +0100 3559044 http://www.medworm.com/index.php?rid=3559043&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455867%26dopt%3DAbstract Authors: McGeown WJ, Shanks MF, Forbes-McKay KE, Waiter GD, Elrick I, Venneri MG, Venneri A Neuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer's disease (AD) have shown the different short and long term actions of ChEIs. fMRI studies of the ChEI donepezil have focused on its short to medium term action without exploring the effects of established treatment. In this exploratory study the effect of 20 weeks donepezil treatment on regional brain activity was measured with fMRI in patients with mild AD. Twelve patients with probable AD and nine age-matched controls were assessed with a Pyramids and Palm Trees semantic association paradigm and an n-back working memory fMRI paradigm. In the patient group only, the assessment was repeated after 20 weeks of treatmen... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559043 Mon, 10 May 2010 23:00:00 +0100 3559043 http://www.medworm.com/index.php?rid=3559042&cid=s_37006_25_f&fid=37006&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455868%26dopt%3DAbstract In conclusion, our data indicate that M-CSF in CSF could be a putative biomarker for MCI. PMID: 20455868 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3559042 Mon, 10 May 2010 23:00:00 +0100 3559042