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. Sun, 21 Mar 2010 15:30:39 +0100 http://www.medworm.com/index.php?rid=3359389&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%3D20214570%26dopt%3DAbstract Authors: Kahiri DK PMID: 20214570 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3359389 Mon, 01 Feb 2010 00:00:00 +0100 3359389 http://www.medworm.com/index.php?rid=3350799&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%3D20205667%26dopt%3DAbstract Authors: Guo L, Duggan J, Cordeiro MF Alzheimer's disease (AD) is the major cause of dementia in the world. Although the entorhinal cortex and hippocampal complex are best known as the sites of early pathology in AD, increasing evidence shows that the eye, particularly the retina, is also affected. The AD-related changes in the retina are associated with degeneration and loss of neurons, reduction of the retinal nerve fibres, increase in optic disc cupping, retinal vascular tortusity and thinning, and visual functional impairment. Given the fact that evaluating pathologic changes in the brain during life has always been an indirect process, largely shielded from view by the barrier of the skull, the eye can be used as a window into diseases of the brain. Using modern techniques, the ch... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350799 Mon, 01 Feb 2010 00:00:00 +0100 3350799 http://www.medworm.com/index.php?rid=3350798&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%3D20205668%26dopt%3DAbstract Authors: Angelucci F, Spalletta G, di Iulio F, Ciaramella A, Salani F, Colantoni L, Varsi AE, Gianni W, Sancesario G, Caltagirone C, Bossù P Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline with loss of memory. In the last years there has been a great interest on the early phases of AD, trying to identify the pathogenic mechanisms of AD and define early treatment modalities. In particular, Mild Cognitive Impairment (MCI) is attractive because it represents a transitional state between normal aging and dementia, although not all MCI patients automatically convert to AD. The neurotrophin brain-derived neurotrophic factor (BDNF) is critical for survival and function of neurons that degenerate in AD and represents a potential neuroprotective ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350798 Mon, 01 Feb 2010 00:00:00 +0100 3350798 http://www.medworm.com/index.php?rid=3350797&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%3D20205669%26dopt%3DAbstract Authors: Zhang C, Browne A, Kim DY, Tanzi RE Alzheimer's disease (AD) is an insidious and progressive disease with a genetically complex and heterogenous etiology. More than 200 fully penetrant mutations in the amyloid beta-protein precursor (APP), presenilin 1 (or PSEN1), and presenilin 2 (PSEN2) have been linked to early-onset familial AD (FAD). 177 PSEN1 FAD mutations have been identified so far and account for more than approximately 80% of all FAD mutations. All PSEN1 FAD mutations can increase the Abeta42:Abeta40 ratio with seemingly different and incompletely understood mechanisms. A recent study has shown that the 286 amino acid N-terminal fragment of APP (N-APP), a proteolytic product of beta-secretase-derived secreted form of APP (sAPPbeta), could bind the death receptor, DR6... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350797 Mon, 01 Feb 2010 00:00:00 +0100 3350797 http://www.medworm.com/index.php?rid=3350796&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%3D20205670%26dopt%3DAbstract Authors: Parri RH, Dineley TK Elevated amyloid-beta peptide (Abeta) and loss of nicotinic acetylcholine receptors (nAChRs) stand prominently in the etiology of Alzheimer's disease (AD). Since the discovery of an Abeta - nAChR interaction, much effort has been expended to characterize the consequences of high versus low concentrations of Abeta on nAChRs. This review will discuss current knowledge on the subject at the molecular, cellular, and physiological levels with particular emphasis on understanding how Abeta - nAChR interaction may contribute to normal physiological processes as well as the etiology of AD. PMID: 20205670 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350796 Mon, 01 Feb 2010 00:00:00 +0100 3350796 http://www.medworm.com/index.php?rid=3350795&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%3D20205671%26dopt%3DAbstract Conclusions: A complex pattern was observed between pathological and functional markers with respect to disease stage (MCI versus AD) and brain regions. Regional differences over time were evident during disease progression. (11)C-PIB PET and CSF Abeta(42) allowed detection of prodromal stages of AD. Amyloid imaging is useful for early diagnosis and evaluation of new therapeutic interventions in AD. PMID: 20205671 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350795 Mon, 01 Feb 2010 00:00:00 +0100 3350795 http://www.medworm.com/index.php?rid=3350794&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%3D20205672%26dopt%3DAbstract Authors: Darreh-Shori T, Soininen H Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline associated with a deficit in cholinergic function. Inhibitors of acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE), such as donepezil, galantamine or rivastigmine, are widely prescribed as symptomatic treatments for AD. These agents exhibit a wide variation in their pharmacological properties. Here we review clinical data from 1998 to 2009 investigating the effect of different cholinesterase inhibitor treatments on the levels and activities of cholinesterases in the cerebrospinal fluid (CSF) of AD patients. These studies suggest that treatment with rapidly-reversible cholinesterase inhibitors (e.g. donepezil, galantamine, tacrine) are... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350794 Mon, 01 Feb 2010 00:00:00 +0100 3350794 http://www.medworm.com/index.php?rid=3350793&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%3D20205673%26dopt%3DAbstract Authors: Zerovnik E The whole set of so-called >>conformational<< disorders, among them systemic amyloidoses, various dementias and other neurodegenerative diseases such as Parkinson's, Alzheimer's and amyotropic lateral sclerosis, may have similar molecular backgrounds: changes in protein conformation and aggregation lead to toxic amyloid oligomers and fibrils. The so called aggresomes in eukaryotes (equivalent to inclusion bodies in prokaryotes), located at the centriole by the nucleus and composed of aggregated proteins, are believed to sequester the toxic material. They eventually get cleared from the cell by autophagy. When the cell defence system fails due to continuous production of a mutated protein or to other damage to the cell such as oxidative stress or protein ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350793 Mon, 01 Feb 2010 00:00:00 +0100 3350793 http://www.medworm.com/index.php?rid=3350792&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%3D20205674%26dopt%3DAbstract Authors: Tsamis IK, Mytilinaios GD, Njau NS, Fotiou FD, Glaftsi S, Costa V, Baloyannis JS CA3 pyramidal neurons and hilar mossy neurons possess large and branched dendritic spines, named thorny excrescences. Studies on experimental animals have shown great morphologic adaptation of the excrescences and the whole dendritic tree of CA3 pyramidal neurons in changes of environmental conditions. However, the available data about the excrescences in human brain is short and insufficient about their properties in Alzheimer's disease. In the present study, these dendritic structures were studied and compared in CA3 area of hippocampus in patients suffered from Alzheimer's disease, age matched controls and young individuals. Golgi impregnated material under light microscopy was used for the des... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350792 Mon, 01 Feb 2010 00:00:00 +0100 3350792 http://www.medworm.com/index.php?rid=3350791&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%3D20205675%26dopt%3DAbstract Authors: Llewellyn DJ, Langa KM, Friedland RP, Lang IA Results from clinical samples suggest low serum albumin may be associated with cognitive impairment, though evidence from population-based studies is inconclusive. Participants were 1,752 adults (699 men and 1,053 women) aged 65 years and over from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum albumin quartiles to cognitive impairment was modelled using logistic regression. Two hundred and twelve participants were cognitively impaired (68 men and 144 women). Odds ratios (95% confidence intervals) for cognitive impairment in the first (2.2-3.8 g/dl), second (3.9-4.0 g/dl), and thi... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3350791 Mon, 01 Feb 2010 00:00:00 +0100 3350791 http://www.medworm.com/index.php?rid=3198344&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%3D20088802%26dopt%3DAbstract Authors: Augelli-Szafran CE, Wei HX, Lu D, Zhang J, Gu Y, Yang T, Wolfe MS Overwhelming evidence supports a central role for the amyloid beta-peptide (Abeta) in the pathogenesis of Alzheimer's disease (AD), and the proteases that produce Abeta from its precursor protein APP are top targets for therapeutic intervention. Considerable effort has focused on targeting gamma-secretase, which generates the C-terminus of Abeta; however, gamma-secretase inhibitors cause serious toxicities due to interference with the Notch signaling pathway. We have been working toward compounds that directly alter gamma-secretase activity to reduce Abeta production without affecting the proteolysis of Notch. Using purified enzyme and substrate, we have shown that gamma-secretase can be selectively inhibited in... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198344 Thu, 21 Jan 2010 00:00:00 +0100 3198344 http://www.medworm.com/index.php?rid=3198343&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%3D20088803%26dopt%3DAbstract Authors: Williams P, Sorribas A, Liang Z Despite the long history of drug discovery from natural sources, the marine environment, which covers 70% of the Earth's surface, is still relatively unexplored. Intense competition for limited resources drives the evolution of specific and potent chemical defenses distinct from their terrestrial counterparts. Based on this rationale, we recently began screening extracts derived from marine invertebrate and cyanobacterial samples for BACE-1 inhibitors in a chemiluminescent enzyme-fragment complementation (EFC) assay. The results of this broad screening are presented here, along with our progress towards the development of a secondary LC-MS homogeneous affinity assay. Incubation of the extracts active in the EFC assay with BACE1, subsequent isola... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198343 Thu, 21 Jan 2010 00:00:00 +0100 3198343 http://www.medworm.com/index.php?rid=3198342&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%3D20088804%26dopt%3DAbstract Authors: Marr RA, Spencer BJ The accumulation of the amyloid-beta peptide (Abeta) continues to emerge as a central factor in Alzheimer's disease (AD). In recent years attention has been drawn to clearance mechanisms of Abeta as evidence suggests reduced clearance may be linked to late-onset AD. Direct degradation of Abeta by endopeptidases has emerged as one critical pathway of clearance. Of particular interest are endopeptidases that are sensitive to the neprilysin inhibitors thiorphan and phosphoramidon (i.e. "NEP-like") as these inhibitors induce a dramatic increase in Abeta levels resulting in rapid plaque formation in wild-type rodents. This review focuses on neprilysin (NEP) and on another NEP-like endopeptidase termed neprilysin-2 (NEP2). The involvement of these endopeptidases ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198342 Thu, 21 Jan 2010 00:00:00 +0100 3198342 http://www.medworm.com/index.php?rid=3198341&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%3D20088805%26dopt%3DAbstract Authors: Kim S, Jensen JR, Cisek K, Funk KE, Naphade S, Schafer K, Kuret J Alzheimer's disease is diagnosed by postmortem detection of pathological lesions that accumulate in specific brain regions. Although the presence of both beta-amyloid plaques and tau-bearing neurofibrillary lesions defines Alzheimer's disease, the distribution of neurofibrillary lesions alone correlates strongly with neurodegeneration and cognitive decline. A whole-brain imaging test capable of detecting these lesions in premortem cases could have great potential for staging and differentially diagnosing Alzheimer's disease. Here we discuss the challenges in developing a whole-brain imaging approach for detection of this intracellular target. PMID: 20088805 [PubMed - as supplied by publisher] (Source: Curren... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198341 Thu, 21 Jan 2010 00:00:00 +0100 3198341 http://www.medworm.com/index.php?rid=3198340&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%3D20088806%26dopt%3DAbstract Authors: Kallmerten AE, Jones GB Positron emission tomography (PET) imaging of Alzheimer's Disease (AD) offers the potential to provide early onset diagnosis and subsequent intervention, including guided treatment regimens. One of the restricting factors in clinical application of PET technology is the limited availability of radioligands with affinity to specific targets of interest. Given the short half-life of the most popular positron emitter currently used ((18)F; approximately 120 min.) extremely rapid and efficient radiochemistry methods are needed to ensure required compounds are prepared and purified for administration within the 2-3 half life practical limit. Recent efforts to combine microwave mediated synthesis with advanced catalysis in the synthesis of specific categories... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198340 Thu, 21 Jan 2010 00:00:00 +0100 3198340 http://www.medworm.com/index.php?rid=3198339&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%3D20088807%26dopt%3DAbstract Authors: Duff K, Kuret J, Congdon EE Tau aggregation is an appealing target for therapeutic intervention. However, conformational change or aggregation needs to be targeted without inhibiting the normal biology of tau and its role in microtubule stabilization. The number of compound classes being tested at this time are very limited and include Congo red derivatives [2], anthraquinones (Pickhardt et al. 2005 [3], disputed in Crowe et al. 2007 [4]), 2,3-di(furan-2-yl)-quinoxalines , phenylthiazolyl-hydrazide (PTH) [5], polyphenols and porphyrins [6] and cyanine dyes [1, 7, 8]. Herein we have utilized a member of the cyanine dye family (C11) in an organotypic slice culture model of tangle formation. Our results demonstrate that C11 is capable of affecting tau polymerization in a biphasic... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198339 Thu, 21 Jan 2010 00:00:00 +0100 3198339 http://www.medworm.com/index.php?rid=3198338&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%3D20088808%26dopt%3DAbstract Authors: Kasturirangan S, Sierks M Accumulation and deposition of beta amyloid (Abeta) play a critical role in the pathogenesis of Alzheimer's Disease (AD), and numerous approaches to control Abeta aggregation are being actively pursued. Brain Abeta levels are controlled by the action of several proteolytic enzymes such as neprilysin (NEP), insulin degrading enzyme (IDE) and plasmin. While up-regulation of these enzymes increased clearance of Abeta in transgenic mouse models of AD, these enzymes have other natural substrates and multiple cleavage sites in Abeta complicating their use for treating AD. Alternatively, immunotherapeutic approaches to clear Abeta are gaining interest. Active and passive immunization studies with Abeta can reduce plaque burden and memory loss, but clinical t... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198338 Thu, 21 Jan 2010 00:00:00 +0100 3198338 http://www.medworm.com/index.php?rid=3198337&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%3D20088809%26dopt%3DAbstract Authors: Malter JS, Ray BC, Westmark PR, Westmark CJ As the mechanisms underlying neuronal development and degeneration become clarified, a number of common effectors and signaling pathways are becoming apparent. Here we describe the identification of Abeta, long considered a pathologic mediator of Alzheimers Disease and Down Syndrome, as similarly over-expressed in the neurodevelopmental disease, Fragile X Syndrome. We also show that mGluR5 inhibitors, currently employed for the treatment of Fragile X, reduce Abeta production in rodent models of Fragile X and AD as well as reduce disease phenotypes including seizures. Thus seemingly disparate neurologic diseases may share a common pathologic instigator and be treatable with a common, currently available class of therapeutics. PMID... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198337 Thu, 21 Jan 2010 00:00:00 +0100 3198337 http://www.medworm.com/index.php?rid=3198336&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%3D20088810%26dopt%3DAbstract Authors: Yurko-Mauro K Memory loss is a prominent health concern, second only to heart disease for older individuals. Docosahexaenoic acid (DHA), the principle omega-3 fatty acid in brain and heart, plays an important role in neural and cardiac function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly and Alzheimer's patients. Higher DHA intake and plasma levels are inversely correlated with increased relative risk of Alzheimer's disease (AD) and fatal coronary heart disease. DHA provides well known cardiovascular benefits (e.g. lower triglycerides, increased HDL cholesterol, decreased resting heart rate) in older adults. Preclinically, DHA supplementation restores brain DHA levels, enhances learning and memory tasks in aged animals, and significantly r... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198336 Thu, 21 Jan 2010 00:00:00 +0100 3198336 http://www.medworm.com/index.php?rid=3198335&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%3D20088811%26dopt%3DAbstract Authors: Gallagher M, Bakker A, Yassa MA, Stark CE Risk for Alzheimer's disease escalates dramatically with increasing age in the later decades of life. It is widely recognized that a preclinical condition in which memory loss is greater than would be expected for a person's age, referred to as amnestic mild cognitive impairment, may offer the best opportunity for intervention to treat symptoms and modify disease progression. Here we discuss a basis for age-related memory impairment, first discovered in animal models and recently isolated in the medial temporal lobe system of man, that offers a novel entry point for restoring memory function with the possible benefit in slowing progression to Alzheimer's disease. PMID: 20088811 [PubMed - as supplied by publisher] (Source: Current A... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198335 Thu, 21 Jan 2010 00:00:00 +0100 3198335 http://www.medworm.com/index.php?rid=3198334&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%3D20088812%26dopt%3DAbstract Authors: Bamburg JR, Bernstein BW, Davis RC, Flynn KC, Goldsbury C, Jensen JR, Maloney MT, Marsden IT, Minamide LS, Pak CW, Shaw AE, Whiteman I, Wiggan O PMID: 20088812 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198334 Thu, 21 Jan 2010 00:00:00 +0100 3198334 http://www.medworm.com/index.php?rid=3198333&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%3D20088813%26dopt%3DAbstract Authors: Coin A, Perissinotto E, Najjar M, Girardi A, Inelmen EM, Enzi G, Manzato E, Sergi G BACKGROUND: several studies have shown that religiosity has beneficial effects on health, mortality and pathological conditions; little is known about religiosity in Alzheimer's disease and the progression of its cognitive, behavioral and functional symptoms. Our aim was to identify any relationship between religiosity and the progression of cognitive impairment and behavioral disorders in mild-moderate Alzheimer's disease, and any relationship between the patient's religiosity and the stress in caregivers. MATERIALS AND METHODS: 64 patients with Alzheimer's disease were analyzed at baseline and 12 months later using the Mini-Mental State Examination (MMSE), the Behavioral Religiosity Scale (BR... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3198333 Thu, 21 Jan 2010 00:00:00 +0100 3198333 http://www.medworm.com/index.php?rid=3136769&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%3D20043808%26dopt%3DAbstract Authors: Fernàndez-Busquets X, Ponce J, Bravo R, Arimon M, Martianyez T, Gella A, Cladera J, Durany N One mechanism leading to neurodegeneration during Alzheimer's disease (AD) is amyloid beta peptide (Abeta)-induced neurotoxicity. Among the factors proposed to potentiate Abeta toxicity is its covalent modification through carbohydrate-derived advanced glycation endproducts (AGEs). Other experimental evidence, though, indicates that certain polymeric carbohydrates like the glycosaminoglycan (GAG) chains found in proteoglycan molecules attenuate the neurotoxic effect of Abeta in primary neuronal cultures. Pretreatment of the 42-residue Abeta fragment (Abeta1-42) with the ubiquitous brain carbohydrates, glucose, fructose, and the GAG chondroitin sulfate B (CSB) inhibits Abeta1-42-in... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136769 Thu, 31 Dec 2009 00:00:00 +0100 3136769 http://www.medworm.com/index.php?rid=3136768&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%3D20043809%26dopt%3DAbstract Authors: Chen B, Bromley-Brits K, He G, Cai F, Zhang X, Song W Cannabinoids have been shown to increase neurogenesis in adult brain, as well as protect neurons from excitotoxicity, calcium influx, inflammation, and ischemia. Recent studies have shown that synthetic cannabinoids can alleviate water maze impairments in rats treated with intracranial amyloid beta protein (Abeta); however it is unknown whether this effect is due to the cannabinoids' anti-inflammatory properties or whether it affects Abeta processing. Here we investigate whether cannabinoids have any effect on Alzheimer's disease in vivo. We found that HU210, a potent synthetic cannabinoid, did not improve water maze performance or a contextual fear conditioning task in an APP23/PS45 double transgenic mouse model of AD. HU2... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136768 Thu, 31 Dec 2009 00:00:00 +0100 3136768 http://www.medworm.com/index.php?rid=3136767&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%3D20043810%26dopt%3DAbstract In conclusion, our data show that osAbeta alters hippocampal network activity at concentrations commonly observed in AD patients and that such effect of osAbeta increase with age. PMID: 20043810 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136767 Thu, 31 Dec 2009 00:00:00 +0100 3136767 http://www.medworm.com/index.php?rid=3136766&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%3D20043811%26dopt%3DAbstract In conclusion, our results suggest that serum NOx-induced lipid oxidation levels were increased in AD and use of antipsychotic drugs may cause lower ox-LDL levels in patients having combination therapy with ChEi's. However, it is required further studies for the determination of clinical importance of these markers. PMID: 20043811 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136766 Thu, 31 Dec 2009 00:00:00 +0100 3136766 http://www.medworm.com/index.php?rid=3136765&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%3D20043812%26dopt%3DAbstract Authors: Spies PE, Slats D, Sjögren JM, Kremer BP, Verhey FR, Rikkert MG, Verbeek MM Background: Amyloid beta(40) (Abeta(40)) is the most abundant Abeta peptide in the brain. The cerebrospinal fluid (CSF) level of Abeta(40) might therefore be considered to most closely reflect the total Abeta load in the brain. Both in Alzheimer's disease (AD) and in normal aging the Abeta load in the brain has a large inter-individual variability. Relating Abeta(42) to Abeta(40) levels might consequently provide a more valid measure for reflecting the change in Abeta metabolism in dementia patients than the CSF Abeta(42) concentrations alone. This measure may also improve differential diagnosis between AD and other dementia syndromes, such as vascular dementia (VaD), dementia with Lewy bodies (DL... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136765 Thu, 31 Dec 2009 00:00:00 +0100 3136765 http://www.medworm.com/index.php?rid=3136764&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%3D20043813%26dopt%3DAbstract Authors: Mancini M, Mancini M, Amenta F The main data on oral health and dental pathologies affecting Alzheimer's disease (AD) patients were reviewed. Oral health declines and dental pathologies increase with progression of AD. Poor oral hygiene, difficulty in wearing dentures, and the inability to self-care, including carrying out oral hygiene procedures are the most probable cause of impaired oral health in AD. Collection of information on oral/dental conditions from AD patients or their caregivers/relatives is often difficult and scientific literature on the topic is sparse . The majority of data on the subject consist in retrospective studies affected to some extent by subjective views of dental professionals involved. Appropriate dental interventions in adult-onset dementia disord... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136764 Thu, 31 Dec 2009 00:00:00 +0100 3136764 http://www.medworm.com/index.php?rid=3136763&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%3D20043814%26dopt%3DAbstract Authors: Avramovich-Tirosh Y, Bar-Am O, Amit T, Youdim MB, Weinreb O Based on a multimodal drug design paradigm, we have synthesized a multifunctional non-toxic, brain permeable iron chelator, M30, possessing the neuroprotective propargylamine moiety of the anti-Parkinsonian drug, rasagiline (Azilect) and antioxidant-iron chelator moiety of an 8-hydroxyquinoline derivative of our iron chelator, VK28. M30 was recently found to confer potential neuroprotective effects in vitro and in various preclinical neurodegenerative models and regulate the levels and processing of the Alzheimer's amyloid precursor protein and its toxic amyloidogenic derivative, Abeta. Here, we show that M30 activates the hypoxia-inducible factor (HIF)-1alpha signaling pathway, thus promoting HIF-1alpha mRNA and prot... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136763 Thu, 31 Dec 2009 00:00:00 +0100 3136763 http://www.medworm.com/index.php?rid=3136762&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%3D20043815%26dopt%3DAbstract The objective was to characterize the non-oscillatory independent components (ICs) of the auditory event-related potential (ERP) waveform of an oddball task for normal and newly diagnosed Alzheimer's disease (AD) subjects, and to seek biomarkers for AD. Single trial ERP waveforms were analysed using independent components analysis (ICA) and k-means clustering. Two stages of clustering depended upon the magnitudes and latencies, and the scalp topographies of the non-oscillatory back-projected ICs (BICs) at electrode Cz. The electrical current dipole sources of the BICs were located using Low Resolution Electromagnetic Tomography (LORETA). Generally 3-10 BICs, of different latencies and polarities, occurred in each trial. Each peak was associated with positive and negative BICs. The trial-to... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136762 Thu, 31 Dec 2009 00:00:00 +0100 3136762 http://www.medworm.com/index.php?rid=3136761&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%3D20043816%26dopt%3DAbstract Authors: Maher-Edwards G, Zvartau-Hind M, Hunter AJ, Gold M, Hopton G, Jacobs G, Davy M, Williams P Background: This randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of the 5-HT6 receptor antagonist, SB-742457, in subjects with mild-to-moderate probable Alzheimer's disease (AD). Methods: Participating subjects had a Mini-Mental State Examination (MMSE) score of 12 to 26 after a 4-week, single-blind, placebo run-in phase, and were randomized (2:1:1:2) to receive placebo, SB-742457 5 mg, 15 mg, or 35 mg once daily for 24 weeks. Coprimary efficacy endpoints were the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+) score and change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) s... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136761 Thu, 31 Dec 2009 00:00:00 +0100 3136761 http://www.medworm.com/index.php?rid=3136760&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%3D20043817%26dopt%3DAbstract Authors: Jost A, Neumann E, Himmelmann KH Processes of demographic change are leading to decreasing human resources in professional as well as lay care; this decrease necessitates new concepts of care, especially for the growing number of people with dementia (p.w.d.). Since the amendment to the German Care Insurance Law (2002), family carers have been entitled to regular weekly relief, provided by volunteers who have been given a thirty-hour-training. As difficulties in information processing in p.w.d. form an important part of the symptoms in dementia sufferers - with a high impact on communication as well as competent functioning in activities associated with daily life -, we wanted to establish how much awareness and sensitivity voluntary attendants show in "tuning in" to the p.w.d... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=3136760 Thu, 31 Dec 2009 00:00:00 +0100 3136760 http://www.medworm.com/index.php?rid=2753346&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%3D19715544%26dopt%3DAbstract Authors: Shytle RD, Bickford PC, Rezai-Zadeh K, Houb L, Zeng J, Tana J, Sanberg PR, Sanberg CD, Roschek B, Fink RC, Alberte RS Inhibition of beta-amyloid (Abeta) accumulation and Abeta fibril (fAbeta) formation from Abeta are attractive therapeutic targets for the treatment of Alzheimer's disease (AD). While previous studies have shown anti-amyloidogenic effects of curcumin in vitro and in vivo, no studies have examined optimized turmeric extracts enriched in curcuminoids or turmerones. Three standardized turmeric extracts, HSS-838, HSS-848, and HSS-888, were prepared with different chemical profiles to investigate their potential therapeutic benefits for AD. These extracts were fingerprinted by DART TOF-MS to reveal the significant chemical complexity. In addition four curcuminoids (c... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753346 Wed, 02 Sep 2009 15:00:28 +0100 2753346 http://www.medworm.com/index.php?rid=2753345&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%3D19715545%26dopt%3DAbstract Authors: Guo L, Duggan J, Cordeiro MF Alzheimer's disease (AD) is the major cause of dementia in the world. Although the entorhinal cortex and hippocampal complex are best known as the sites of early pathology in AD, increasing evidence shows that the eye, particularly the retina, is also affected. The AD-related changes in the retina are associated with degeneration and loss of neurons, reduction of the retinal nerve fibres, increase in optic disc cupping, retinal vascular tortusity and thinning, and visual functional impairment. Given the fact that evaluating pathologic changes in the brain during life has always been an indirect process, largely shielded from view by the barrier of the skull, the eye can be used as a window into diseases of the brain. Using modern techniques, the ch... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753345 Wed, 02 Sep 2009 15:00:26 +0100 2753345 http://www.medworm.com/index.php?rid=2753344&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%3D19715546%26dopt%3DAbstract Authors: Angelucci F, Spalletta G, di Iulio F, Ciaramella A, Salani F, Colantoni L, Varsi AE, Gianni W, Sancesario G, Caltagirone C, Bossù P Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline with loss of memory. In the last years there has been a great interest on the early phases of AD, trying to identify the pathogenic mechanisms of AD and define early treatment modalities. In particular, Mild Cognitive Impairment (MCI) is attractive because it represents a transitional state between normal aging and dementia, although not all MCI patients automatically convert to AD. The neurotrophin brain-derived neurotrophic factor (BDNF) is critical for survival and function of neurons that degenerate in AD and represents a potential neuroprotective ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753344 Wed, 02 Sep 2009 15:00:23 +0100 2753344 http://www.medworm.com/index.php?rid=2753343&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%3D19715547%26dopt%3DAbstract Authors: Grabowska I, Radecka H, Burza A, Radecki J, Kaliszan M, Kaliszan R Amyloid beta(1-40) peptide was immobilized on an Au-colloid modified gold electrode and an electrochemical impedance spectroscopy (EIS) system was elaborated for determining the association constants, K(a), between small molecular ligands and the peptide. The changes in the resistance of the modified electrode layer with deposited Abeta(1-40) peptide were measured with EIS in relation to a series of concentrations of the ligands studied. The association constants were calculated from Langmuir isotherms. The method is sensitive, reproducible and consumes only very little amounts of interacting species. The method was applied to determine the affinity of a series of pyridine and piperidine derivatives, mainly alk... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753343 Wed, 02 Sep 2009 15:00:21 +0100 2753343 http://www.medworm.com/index.php?rid=2753342&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%3D19715548%26dopt%3DAbstract CONCLUSIONS: Accumulation of neuropathology appears to correlate with functional, global, and cognitive decline as people progress from MCI through AD. PMID: 19715548 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753342 Wed, 02 Sep 2009 15:00:18 +0100 2753342 http://www.medworm.com/index.php?rid=2753341&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%3D19715549%26dopt%3DAbstract Authors: Zhang C, Browne A, Kim DY, Tanzi RE Alzheimer's disease (AD) is an insidious and progressive disease with a genetically complex and heterogenous etiology. More than 200 fully penetrant mutations in the amyloid beta-protein precursor (APP), presenilin 1 (or PSEN1), and presenilin 2 (PSEN2) have been linked to early-onset familial AD (FAD). 177 PSEN1 FAD mutations have been identified so far and account for more than approximately 80% of all FAD mutations. All PSEN1 FAD mutations can increase the Abeta42:Abeta40 ratio with seemingly different and incompletely understood mechanisms. A recent study has shown that the 286 amino acid N-terminal fragment of APP (N-APP), a proteolytic product of beta-secretase-derived secreted form of APP (sAPPbeta), could bind the death receptor, DR6... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753341 Wed, 02 Sep 2009 15:00:16 +0100 2753341 http://www.medworm.com/index.php?rid=2753340&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%3D19715550%26dopt%3DAbstract Authors: Vestergaard M, Hamada T, Morita M, Takagi M High levels of cholesterol have been proposed as a risk factor for Alzheimer's disease (AD). Polymorphism of genes encoding proteins that regulate cholesterol metabolism have also been associated with the frequency of Alzheimer's development. Some studies have shown that cholesterol-lowering drugs reduce the frequency of AD development. The proposed role of cholesterol in AD has been challenged by several studies. In this review, we provide a brief account of the major pieces of evidence in support of and against the possible role of cholesterol in the development of AD, and the methodologies used. We highlight the interactions between cholesterol and amyloid beta (Abeta) and, with the peptide's precursor protein. Drawing from our te... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753340 Wed, 02 Sep 2009 15:00:14 +0100 2753340 http://www.medworm.com/index.php?rid=2753339&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%3D19715551%26dopt%3DAbstract Curr Alzheimer Res. 2009 Dec 1; Authors: Gorham P, Bark N, Björkhem , Meaney S, Crisby M The processing of the Amyloid Precursor Protein (APP) is a critical event in the formation of amyloid plaques which are composed of the 4kDa amyloid beta-peptide (Abeta). Processing of APP occurs through a non-amyloidogenic pathway, mediated by initial alpha-secretase cleavage or through an amyloidogenic pathway via sequential cleavage by beta- and gamma-secretase enzymes, which produces Abeta peptides. Currently, the diagnosis of probable or possible Alzheimer's disease (AD) is primarily based on neuropsychological and neuroradiological assessment. Recent reports indicate that platelet beta-secretase activity is moderately increased in patients with AD and mild cognitive impairment (MCI).... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753339 Wed, 02 Sep 2009 15:00:10 +0100 2753339 http://www.medworm.com/index.php?rid=2753338&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%3D19715552%26dopt%3DAbstract Conclusion: The HUI-III findings suggest that health utilities could be combined with other known correlates of costs to inform resource allocation cost-effectiveness analyses associated with AD. The ADRQoL findings suggest that better quality of life may make it easier for caregivers to identify problems and/or to access and maintain certain types of health system contacts. PMID: 19715552 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753338 Wed, 02 Sep 2009 15:00:08 +0100 2753338 http://www.medworm.com/index.php?rid=2753337&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%3D19715553%26dopt%3DAbstract Authors: Borroni B, Costanzi C, Padovani A Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline including loss of memory, orientation and reasoning. However, a relevant aspect of AD is the presence of a variety of behavioural and psychological symptoms in dementia (BPSD), beyond the well-known progressive cognitive impairment. Approximately 50% to 80% of patients diagnosed with AD present behavioural or psychiatric disturbances such as psychosis, depression, agitation, disinhibition, aggression, hyperactivity, and socially intrusive behaviours. These symptoms may be burdensome for physicians and caregivers and lead to earlier institutionalization and increased social and economic costs. In this view, recent literature has considered th... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2753337 Wed, 02 Sep 2009 15:00:05 +0100 2753337 http://www.medworm.com/index.php?rid=2692827&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%3D19663793%26dopt%3DAbstract Authors: Gozes I, Stewart A, Morimoto B, Fox A, Sutherland K, Schmeche D AL-108 is the intranasal formulation of NAP (a peptide of eight amino acids, NAPVSIPQ). Phase IIa clinical results have recently shown that AL-108 has a positive impact on memory function in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease (AD). The clinical development of AL-108 has been based on extensive studies showing pre-clinical efficacy for NAP. NAP has demonstrated potent neuroprotective activity in vitro and in vivo. Its mechanism of action is thought to center on the modulation of microtubule stability in the face of outside damage. Such an effect on structures of such central importance in a broad range of cellular functions is thought to explain NAP's activit... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692827 Thu, 13 Aug 2009 09:22:25 +0100 2692827 http://www.medworm.com/index.php?rid=2692826&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%3D19663794%26dopt%3DAbstract Authors: Yuzwa SA, Vocadlo DJ The aggregation of the microtubule-associated protein tau into paired-helical filaments is the defining characteristic of the tauopathies. It has become apparent that the hyperphosphorylation of tau likely plays a role in the aggregation process and thus strategies to reduce tau phosphorylation are generating wide interest. The O-GlcNAc posttranslational modification of tau has been shown to be reciprocal to its phosphorylation; increasing O-GlcNAc leads to reductions in tau phosphorylation. In this mini-review, we highlight the use of chemical compounds as a means of understanding the reciprocal nature of tau phosphorylation and tau O-GlcNAcylation and highlight some recent progress in this area. PMID: 19663794 [PubMed - as supplied by publisher] (Sou... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692826 Thu, 13 Aug 2009 09:22:21 +0100 2692826 http://www.medworm.com/index.php?rid=2692825&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%3D19663795%26dopt%3DAbstract Authors: Sigurdsson EM Immunotherapies targeting the amyloid-beta (Abeta) peptide in Alzheimer's disease (AD) have consistently been effective in mouse studies and shown promise in clinical trials, although some setbacks have occurred. First, encephalitis was observed in a small subset of patients. More recent autopsy data from a few subjects suggests that clearance of Abeta plaques may not halt cognitive deterioration once impairments are evident, emphasizing the need for other more effective approaches at that stage of the disease. Another important target in AD is the neurofibrillary tangles and its precursors, composed primarily of hyperphosphorylated tau proteins, which correlate well with the degree of dementia. As Abeta and tau pathologies are likely synergistic, targeting both ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692825 Thu, 13 Aug 2009 09:22:19 +0100 2692825 http://www.medworm.com/index.php?rid=2692824&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%3D19663796%26dopt%3DAbstract Authors: Bahr BA Protein accumulation leads to CNS effects in Alzheimer's disease, frontotemporal dementia, and other agerelated disorders. Common mechanisms may contribute to the progressive pathology in the different protein accumulation disorders, and synergistic toxicity between dissimilar protein structures may also be involved. Among several avenues being pursued to reduce proteins prone to oligomerization and/or aggregation, a lysosomal avenue has been described that regulates the lysosomal system's broad clearance capability. Lysosomes are the primary site for protein clearance, to remove old and misfolded proteins and maintain cellular homeostasis. Small-molecule lysosomal modulators trigger a feedback response in vitro and in vivo, resulting in marked up-regulation of catheps... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692824 Thu, 13 Aug 2009 09:22:16 +0100 2692824 http://www.medworm.com/index.php?rid=2692823&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%3D19663797%26dopt%3DAbstract In this study we tested the effects of the selective PPARdelta agonist GW742 in 5xFAD mice which harbor 3 mutations in amyloid precursor protein and 2 mutations in presenilin 1, develop plaques by 5-6 weeks of age, and show robust inflammation and neuronal damage. Oral delivery of GW742 significantly reduced amyloid plaque burden in the subiculum region of 3-month old male and female 5xFAD mice. GW742 also significantly reduced astrocyte activation, suggesting anti-inflammatory effects on glia cells. The changes in plaque burden were accompanied by increased expression of the amyloid degrading enzymes neprilysin and insulin degrading enzyme, while in transfected HEK293 cells, GW742 activated a neprilysin promoter driving luciferase expression. These results suggest that, as found for some ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692823 Thu, 13 Aug 2009 09:22:14 +0100 2692823 http://www.medworm.com/index.php?rid=2692822&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%3D19663798%26dopt%3DAbstract Authors: Schipper HM, Gupta A, Szarek WA The mechanisms responsible for oxidative damage, pathological brain iron deposition and mitochondrial insufficiency in Alzheimer disease (AD) remain enigmatic. Heme oxygenase-1 (HO-1) is a 32 kDa stress protein that catabolizes heme to biliverdin, free iron and carbon monoxide. The HO-1 gene is exquisitely sensitive to oxidative stress and is induced in brain and other tissues in various models of disease and trauma. Our laboratory demonstrated that 1) HO-1 protein is significantly over-expressed in AD-affected temporal cortex and hippocampus relative to neurohistologicallynormal control preparations, 2) in cultured astrocytes, HO-1 up-regulation by transient transfection of the human ho-1 gene, or stimulation of endogenous HO-1 expression by ex... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692822 Thu, 13 Aug 2009 09:22:12 +0100 2692822 http://www.medworm.com/index.php?rid=2692821&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%3D19663799%26dopt%3DAbstract Authors: Saragovi HU, Hamel E, Di Polo A The concept and rationale for neuroprotection are presented. Several examples of small molecule neurotrophic agents with favourable drug-like and pharmacological properties are shown. Compound efficacy in acute neurodegenerative models (optic nerve axotomy) and chronic neurodegenerative models (glaucoma, age-associated cognitive impairment, Alzheimer's Disease) are evaluated and discussed. Targeting neurotrophin receptors with ligands that activate survival pathways or inhibit death pathways is an alternative worth pursuing. PMID: 19663799 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692821 Thu, 13 Aug 2009 09:22:09 +0100 2692821 http://www.medworm.com/index.php?rid=2692820&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%3D19663800%26dopt%3DAbstract We present evidence that domain interaction results in stressed astrocytes that are dysfunctional and propose that dysfunctional astrocytes are an early player in apoE4-associated AD and that domain interaction is a potential therapeutic target. PMID: 19663800 [PubMed - as supplied by publisher] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692820 Thu, 13 Aug 2009 09:22:07 +0100 2692820 http://www.medworm.com/index.php?rid=2692819&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%3D19663801%26dopt%3DAbstract Authors: Chang E, Honson NS, Bandyopadhyay B, Funk KE, Jensen JR, Kim S, Naphade S, Kuret J Recent results from high-throughput and other screening approaches reveal that small molecules can directly interact with recombinant full-length tau monomers and fibrillar tau aggregates in three distinct modes. First, in the high concentration regime (>10 micromolar), certain anionic molecules such as Congo red efficiently promote tau filament formation through a nucleation-elongation mechanism involving a dimeric nucleus and monomer-mediated elongation. These compounds are useful for modeling tau aggregation in vitro and in biological models. Second, in the low concentration regime (<1 micromolar), other ligands, including cyanine dyes, display aggregation antagonist activity. Compounds... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2692819 Thu, 13 Aug 2009 09:22:05 +0100 2692819 http://www.medworm.com/index.php?rid=2534613&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%3D19519300%26dopt%3DAbstract Authors: Souchay C, Moulin CJ Human memory can be split into familiarity and recollection processes which contribute to different aspects of memory function. These separate processes result in different experiential states. In this review, we examine how this dominant theoretical framework can explain the subjective experience of people with Alzheimer's disease, the profile of their memory impairments and their inability to reflect on their performance metacognitively. We conclude with a brief overview of the brain regions supporting conscious experience of memory, and propose that the memory and awareness deficits seen in Alzheimer's disease could be conceived of as a deficit in autonoetic consciousness. A future priority for research is to take these robust constructs into research p... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534613 Sun, 31 May 2009 23:00:00 +0100 2534613 http://www.medworm.com/index.php?rid=2534612&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%3D19519301%26dopt%3DAbstract Authors: Behrens MI, Lendon C, Roe CM Cancer and Alzheimer's disease (AD) are two common disorders for which the final pathophysiological mechanism is not yet clearly defined. In a prospective longitudinal study we have previously shown an inverse association between AD and cancer, such that the rate of developing cancer in general with time was significantly slower in participants with AD, while participants with a history of cancer had a slower rate of developing AD. In cancer, cell regulation mechanisms are disrupted with augmentation of cell survival and/or proliferation, whereas conversely, AD is associated with increased neuronal death, either caused by, or concomitant with, beta amyloid (Abeta) and tau deposition. The possibility that perturbations of mechanisms involved in cell... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534612 Sun, 31 May 2009 23:00:00 +0100 2534612 http://www.medworm.com/index.php?rid=2534611&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%3D19519302%26dopt%3DAbstract Authors: Lopes JP, Oliveira CR, Agostinho P Alzheimer's disease (AD) is an irreversible, progressive brain disease that slowly destroys memory and thinking skills. With over 26 million patients in 2006, AD is the most prevalent neurodegenerative disease worldwide. Different hypotheses have been suggested to explain the pathogenesis of AD, like those involving inflammation, mitochondrial dysfunction or oxidative stress. Many of these studies have addressed amyloid plaque formation, tau hyperphosphorylation and apoptotic neuronal loss, the three main histopathological hallmarks of this disease. Increasing evidences, however, suggest another feature that can also be considered a neuropathological marker for AD: ectopic cell cycle re-entry. Cell cycle events have been frequently registered... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534611 Sun, 31 May 2009 23:00:00 +0100 2534611 http://www.medworm.com/index.php?rid=2534610&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%3D19519303%26dopt%3DAbstract Authors: Freude S, Schilbach K, Schubert M In different clinical studies, an association of type 2 diabetes and Alzheimer's disease (AD) has been described. However, the underlying mechanisms are still unclear. One explanation could be that vascular complications of diabetes result in neurodegeneration. Alternatively, the mechanism might be directly related to insulin and insulin-like growth factor(IGF)-1 signaling, leading to the proposal that AD is a "brain-type diabetes". Furthermore, postmortem analyses of brains from patients with AD revealed a markedly downregulated expression of insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1 and IRS-2, and these changes progress with severity of neurodegeneration. These findings raise the question, whether thi... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534610 Sun, 31 May 2009 23:00:00 +0100 2534610 http://www.medworm.com/index.php?rid=2534608&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%3D19519304%26dopt%3DAbstract Authors: Rocchi A, Orsucci D, Tognoni G, Ceravolo R, Siciliano G Alzheimer's disease (AD) is a late-onset progressive neurodegenerative disorder which results in the irreversible loss of cortical neurons, particularly in the associative neocortex and hippocampus. AD is the most common form of dementia in the elderly. Apart from the neuronal loss, the pathological hallmarks are extracellular senile plaques, containing the peptide beta-amyloid (Abeta), and neurofibrillary tangles. The Abeta cascade hypothesis remains the main pathogenetic model, as suggested by familiar AD, mainly associated to mutation in amyloid precursor protein and presenilin genes. The remaining 95% of AD patients are mostly sporadic late-onset cases, with a complex aetiology due to interactions between environmenta... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534608 Sun, 31 May 2009 23:00:00 +0100 2534608 http://www.medworm.com/index.php?rid=2534607&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%3D19519305%26dopt%3DAbstract Authors: Cimini A, Benedetti E, D'Angelo B, Cristiano L, Falone S, Di Loreto S, Amicarelli F, Cerù MP The central role of peroxisomes in ROS and lipid metabolism and their importance in brain functioning are well established. The aim of this work was to study the modulation of peroxisomal and peroxisome-related proteins in cortical neurons in vitro challenged with chronic or acute Abeta treatment, in order to investigate whether peroxisomes represent one of the cellular target of Abeta in these cells. The expression of peroxisomal (PMP70, catalase, acyl-CoA oxidase and thiolase), peroxisome-related (PPARalpha, insulin-degrading enzyme) and anti-oxidant (SOD1, SOD2, GSTP1) proteins was studied. The results obtained, demonstrating an early upregulation of the peroxisomal proteins du... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534607 Sun, 31 May 2009 23:00:00 +0100 2534607 http://www.medworm.com/index.php?rid=2534606&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%3D19519306%26dopt%3DAbstract Authors: Munishkina LA, Fink AL, Uversky VN To better model the characteristics of crowded intracellular environments, we examined the effect of several factors known to induce partial folding and accelerated fibrillation of alpha-synuclein in dilute solutions, on the fibrillation of this protein in a crowded milieu. We found that low pH, certain metals and pesticides, polyanions, polycations and low concentrations of organic solvents cause a significant acceleration of alpha-synuclein fibrillation in the presence of high concentrations of polyethylene glycol. This suggests that the fibril-promoting effects of factors inducing partial folding of alpha-synuclein and the fibril-stimulating effects of macromolecular crowding are relatively independent and thus might act additively or even... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534606 Sun, 31 May 2009 23:00:00 +0100 2534606 http://www.medworm.com/index.php?rid=2534605&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%3D19519307%26dopt%3DAbstract Authors: Tackenberg C, Ghori A, Brandt R Since their first description by Ramon y Cajal at the end of the 19th century, dendritic spines have been proposed as important sites of neuronal contacts and it has been suggested that changes in the activity of neurons directly affect spine morphology. In fact, since then it has been shown that about 90% of excitatory synapses end on spines. Recent data indicate that spines are highly dynamic structures and that spine shape correlates with the strength of synaptic transmission. Furthermore, several mental disorders including Alzheimer's disease (AD) are associated with spine pathology suggesting that spine alterations play a central role in mental deficits. The aim of this review is to provide an overview about the current knowledge on spine m... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534605 Sun, 31 May 2009 23:00:00 +0100 2534605 http://www.medworm.com/index.php?rid=2534604&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%3D19519308%26dopt%3DAbstract Authors: Soutar MP, Thornhill P, Cole AR, Sutherland C Collapsin response mediator protein-2 (CRMP2) was recently identified as a physiological substrate for GSK3 and Cdk5, two protein kinases suggested to exhibit greater activity in Alzheimer's disease (AD). Indeed, phosphorylation of CRMP2, at the residues targeted by GSK3 and Cdk5, is relatively high in cortex isolated from human AD brain, as well as in the brains of animal models of AD, while phospho-CRMP2 is found in neurofibrillary tangles. In mouse models of AD, increased phosphorylation occurs prior to pathology. Although CRMP2 has no known enzymatic activity, a great deal of information is appearing on its importance in neuronal development and polarity, as well as in axon growth and guidance. In this mini-review, we examine w... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534604 Sun, 31 May 2009 23:00:00 +0100 2534604 http://www.medworm.com/index.php?rid=2534603&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%3D19519309%26dopt%3DAbstract Authors: Papaliagkas VT, Anogianakis G, Tsolaki MN, Koliakos G, Kimiskidis VK The aim of the present study was to investigate the role of CSF cytochrome c levels and auditory event-related potentials (AERPs) on the progress of mild cognitive impairment (MCI) to Alzheimer's disease (AD). Fifty one patients diagnosed with MCI and fourteen healthy individuals underwent lumbar puncture at baseline and their CSF cytochrome c levels were determined. A follow-up examination of cytochrome c levels took place in 20 patients after 11 months and in this period five of the patients progressed to AD. ERP examinations were also performed in all patients both at baseline and follow-up. MCI patients had significantly higher cytochrome c levels compared to healthy controls (Mann-Whitney test, Z=-2.110,... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534603 Sun, 31 May 2009 23:00:00 +0100 2534603 http://www.medworm.com/index.php?rid=2534602&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%3D19519310%26dopt%3DAbstract Authors: Funke SA, Birkmann E, Willbold D Today, the most reliable diagnosis for Alzheimer's disease (AD) is the post mortem identification of amyloid plaques, consisting of the Amyloid-beta (Abeta) peptide, (and neurofibrillary tangles) in the brain of the patient. Great efforts are being made to identify reliable biomarkers for AD that are suitable for minimal invasive early diagnosis and prognosis of AD. During the past years, body fluids of AD patients were assayed for their content of total or soluble Abeta(1-40) or Abeta(1-42) concentrations using classical (ELISA) or non-classical (with additional signal amplification) read-out. Cerebrospinal fluid (CSF) concentrations of soluble Abeta(1-42) are reduced by 40 to 50 % in AD patients compared to age-matched healthy controls as con... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534602 Sun, 31 May 2009 23:00:00 +0100 2534602 http://www.medworm.com/index.php?rid=2534601&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%3D19519311%26dopt%3DAbstract In conclusion, LP performed with a 24g Sprotte atraumatic needle (blunt, "bullet" tip) was a well tolerated procedure, with good acceptability. PMID: 19519311 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534601 Sun, 31 May 2009 23:00:00 +0100 2534601 http://www.medworm.com/index.php?rid=2534600&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%3D19519312%26dopt%3DAbstract Authors: Raglio A, Gianelli MV This contribution focuses on the definition of music therapy as a specific applicative context to be seen as distinct from the generic use of music in a variety of pathologies. Music therapy is presented as a discipline grounded both upon relationship and upon the theoretical-methodological principles peculiar to each applicative model. The therapeutic nature proper to music therapy is highlighted with specific reference to the domain of the dementias. Music therapy facilitates expression, communication and relationship in the non-verbal context. Such an opportunity allows persons with dementia to establish contact, to express, and even contrive an organisation/regulation of their emotions, through the sonorous-musical relationship with the music therapis... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534600 Sun, 31 May 2009 23:00:00 +0100 2534600 http://www.medworm.com/index.php?rid=2534599&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%3D19519313%26dopt%3DAbstract Authors: Shudo K, Fukasawa H, Nakagomi M, Yamagata N Alzheimer's disease(AD) is associated with a variety of pathophysiological features, including amyloid plaques, inflammation, immunological changes, cell death and regeneration processes, altered neurotransmission, and age-related changes. Retinoic acid receptors (RARs) and retinoids are relevant to all of these. Here we review the pathology, pharmacology, and biochemistry of AD in relation to RARs and retinoids, and we suggest that retinoids are candidate drugs for treatment of AD. PMID: 19519313 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534599 Sun, 31 May 2009 23:00:00 +0100 2534599 http://www.medworm.com/index.php?rid=2534598&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%3D19519314%26dopt%3DAbstract Authors: Dimou E, Booij J, Rodrigues M, Prosch H, Attems J, Knoll P, Zajicek B, Dudczak R, Mostbeck G, Kuntner C, Langer O, Bruecke T, Mirzaei S The neurodegenerative disorder Alzheimer's disease (AD) is the most common form of dementia. It is characterized by progressive impairment of cognitive functions and behavior. To distinguish clinically AD from other forms of dementia is an ongoing challenge. In addition, although mild cognitive impairment (MCI) is recognized as a risk factor for dementia, it remains a challenge to predict on an individual level who will convert to become demented. Amyloid beta (Abeta) is one of the crucial pathological findings in AD. Recently, amyloid tracers for PET imaging have been developed successfully which may offer the unique possibility for measuring... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534598 Sun, 31 May 2009 23:00:00 +0100 2534598 http://www.medworm.com/index.php?rid=2534625&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%3D19355842%26dopt%3DAbstract Authors: Martínez A, Lahiri DK, Giacobini E, Greig NH Although significant accomplishments have been made in research to understand, diagnose and treat Alzheimer's disease (AD) and its prequel, mild cognitive impairment, over the last two decades, a huge amount more remains to be achieved to impact this incurable, terminal disease that afflicts an estimated 26.6 million people worldwide. Increasing evidence indicates that early diagnosis will be fundamental to maximizing treatment benefits. Moreover, mechanistically-based, hypothesis-driven treatment strategies are now emerging to hopefully spearhead future therapy. The crossfertilization of ideas from multiple disciplines will prove key to optimize strategies and translate them to meaningful clinical utility, and forms the basis ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534625 Tue, 31 Mar 2009 23:00:00 +0100 2534625 http://www.medworm.com/index.php?rid=2534624&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%3D19355843%26dopt%3DAbstract Authors: Pepeu G, Giovannini MG Cholinesterase inhibitors (ChEIs) were introduced in the therapy of Alzheimer Disease (AD) in the nineteen nineties with great expectations. The hopes and large interest raised by these drugs are well demonstrated by 12,000 references listed by PubMed under 'ChEI' for 1995-2007. The list is reduced to 2500 if we confine ourselves to 'ChEIs and dementia'. Of them, about 500 were published in the last two years. Whereas an increase in brain acetylcholine and an improvement of cognitive deficits have been consistently demonstrated in animal models of AD, from aging rats to transgenic mice, the clinical effectiveness of ChEIs has been and is still a matter of contrasting opinions. These range from the negative conclusions of the AD2000 trial on donepezil, cl... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534624 Tue, 31 Mar 2009 23:00:00 +0100 2534624 http://www.medworm.com/index.php?rid=2534623&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%3D19355844%26dopt%3DAbstract This study aimed to assess the clinically variable ChEI treatment effects in a group of patients with mild AD using a semantic association and an N-back light working memory activation paradigm. Twenty-six patients with probable mild AD treated with a ChEI for 20 weeks were retrospectively divided into responders and non-responders. Patients were classified as responders if their Clinician's Interview Based Impression of Change (CIBIC - Plus) score was four or less and if they had an increase of at least two points on the MMSE. These criteria resulted in two subgroups comprising nine responders and seventeen non responders. Nine healthy elderly age-matched controls were also recruited as a comparison group. ChEI treatment was accompanied by significant modulation of task induced activation... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534623 Tue, 31 Mar 2009 23:00:00 +0100 2534623 http://www.medworm.com/index.php?rid=2534622&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%3D19355845%26dopt%3DAbstract Authors: Caccamo A, Fisher A, LaFerla FM Cholinergic deficit is a cardinal feature of Alzheimer's disease, and cholinesterase inhibitors represent one of the most prominent means of mitigating this dysfunction. Cholinesterase inhibitors provide mild symptomatic relief, although they lose their efficacy over time most likely because they are not disease-modifying agents. An alternative strategy for restoring cholinergic function and attenuating the cognitive decline involves acting on the receptors on which acetylcholine acts. Stimulation of muscarinic acetylcholine receptors and in particular the M1 subtype has been shown to have a beneficial effect in restoring cognition in patients with Alzheimer's disease and in attenuating Abeta and tau pathology in different animal models. In this... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534622 Tue, 31 Mar 2009 23:00:00 +0100 2534622 http://www.medworm.com/index.php?rid=2534621&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%3D19355846%26dopt%3DAbstract CONCLUSION: The combination of GEPT extracts can reduce levels of endogenous Abeta peptide in APPV717I transgenic mice through the inhibition of PS1 activity rather than BACE1 and the promotion of IDE and NEP activity. Lower-expression of PS1 and over-expression of IDE or NEP may be helpful in potentially lowering brain Abeta levels in subjects with AD, and hence GEPT appears to offer potential that should be explored in AD. PMID: 19355846 [PubMed - indexed for MEDLINE] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534621 Tue, 31 Mar 2009 23:00:00 +0100 2534621 http://www.medworm.com/index.php?rid=2534620&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%3D19355847%26dopt%3DAbstract Authors: Ito K, Ishibashi K, Tomiyama T, Umeda T, Yamamoto K, Kitajima E, Idomoto T, Nagatomo T, Mori H Oligomer Abeta is the term utilized for multimeric but non-fibrillar forms of amyloid beta-protein (Abeta). The most prominent property of oligomer Abeta is considered to be its solubility and structure. Here, we examined the histochemical localization of oligomer Abeta in AD brains. At present, little information is available on the structure and function of cerebral oligomer Abeta. We therefore studied the molecular localization of oligomer Abeta using a newly generated polyclonal mouse antisera against a variant Abeta with a deletion mutation of the 22(nd) glutamate that we found recently in a patient with familial Alzheimer's disease. Intracellular as well as extracellular oligom... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534620 Tue, 31 Mar 2009 23:00:00 +0100 2534620 http://www.medworm.com/index.php?rid=2534619&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%3D19355848%26dopt%3DAbstract CONCLUSIONS: The present animal imaging system would substantially facilitate establishment of a safe and effective therapeutic strategy targeting multiple key processes in the AD pathogenesis. PMID: 19355848 [PubMed - indexed for MEDLINE] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534619 Tue, 31 Mar 2009 23:00:00 +0100 2534619 http://www.medworm.com/index.php?rid=2534618&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%3D19355849%26dopt%3DAbstract CONCLUSIONS: Approximately 4.6 years after immunization with AN1792, patients defined as responders in the phase 2a study maintained low but detectable, sustained anti-AN1792 antibody titers and demonstrated significantly reduced functional decline compared with placebo-treated patients. Brain volume loss in antibody responders was not significantly different from placebo-treated patients approximately 3.6 years from the end of the original study. No further cases of encephalitis were noted. These data support the hypothesis that Abeta immunotherapy may have long-term functional benefits. PMID: 19355849 [PubMed - indexed for MEDLINE] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534618 Tue, 31 Mar 2009 23:00:00 +0100 2534618 http://www.medworm.com/index.php?rid=2534617&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%3D19355850%26dopt%3DAbstract Authors: Belarbi K, Schindowski K, Burnouf S, Caillierez R, Grosjean ME, Demeyer D, Hamdane M, Sergeant N, Blum D, Buée L Alzheimer's disease is a neurodegenerative disorder characterized by amyloid deposits and neurofibrillary tangles. Cholinergic dysfunction is also a main pathological feature of the disease. Nevertheless, the links between cholinergic dysfunction and neuropathological hallmarks of Alzheimer's are still unknown. In the present study, we aimed to further investigate Tau aggregation in cholinergic systems, in a Tau transgenic mouse model. THY-Tau22 mice have recently been described as a novel model of Alzheimer-like Tau pathology without motor deficits. This strain presents an age-dependent development of Tau pathology leading to synaptic dysfunctions as well as l... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534617 Tue, 31 Mar 2009 23:00:00 +0100 2534617 http://www.medworm.com/index.php?rid=2534616&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%3D19355851%26dopt%3DAbstract We describe an engineered mutein of hNGF, hNGF-61, that is selectively recognized, against endogenous NGF, by a specific antibody. hNGF-61 mutein has an identical potency and bioactivity profile as hNGF, in vitro and in vivo. Moreover, hNGF-61 and hNGF are equally effective in rescuing the behavioral and neurodegenerative phenotype in adult and aged AD11 anti-NGF mice. Finally, we demonstrated that intranasally delivered hNGF-61 is significantly more effective than ocularly applied hNGF-61, to determine phenotypic rescue in AD11 mice. The development of hNGF-61 towards clinical applications in AD patients is under way. PMID: 19355851 [PubMed - indexed for MEDLINE] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534616 Tue, 31 Mar 2009 23:00:00 +0100 2534616 http://www.medworm.com/index.php?rid=2534615&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%3D19355852%26dopt%3DAbstract Authors: Sarasa M, Pesini P The most common animal models currently used for Alzheimer disease (AD) research are transgenic mice that express a mutant form of human Abeta precursor protein (APP) and/or some of the enzymes implicated in their metabolic processing. However, these transgenic mice carry their own APP and APP-processing enzymes, which may interfere in the production of different amyloid-beta (Abeta) peptides encoded by the human transgenes. Additionally, the genetic backgrounds of the different transgenic mice are a possible confounding factor with regard to crucial aspects of AD that they may (or may not) reproduce. Thus, although the usefulness of transgenic mice is undisputed, we hypothesized that additional relevant information on the physiopathology of AD could be obta... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534615 Tue, 31 Mar 2009 23:00:00 +0100 2534615 http://www.medworm.com/index.php?rid=2534614&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%3D19355853%26dopt%3DAbstract Authors: Pihlajamäki M, Jauhiainen AM, Soininen H Mild cognitive impairment (MCI), and the amnestic subtype of MCI in particular, is the most recent concept used to describe the intermediary state between healthy aging and Alzheimer's disease (AD). It is hoped that research focusing on MCI would yield markers for early identification of individuals with prodromal AD at such a pre-dementia stage when potential disease modifying therapies would be most efficacious. Magnetic resonance imaging (MRI) combined with various data analysis methods provides tools to investigate alterations in brain structure and function in vivo. Structurally, MCI is characterized by atrophy of the medial temporal lobe (MTL) structures such as the hippocampus and entorhinal cortex, and the amount of atrophy... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2534614 Tue, 31 Mar 2009 23:00:00 +0100 2534614 http://www.medworm.com/index.php?rid=2173582&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%3D19199869%26dopt%3DAbstract Authors: Lahiri DK PMID: 19199869 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173582 Sun, 01 Feb 2009 05:00:00 +0100 2173582 http://www.medworm.com/index.php?rid=2173581&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%3D19199870%26dopt%3DAbstract Conclusion: The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation. PMID: 19199870 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173581 Sun, 01 Feb 2009 05:00:00 +0100 2173581 http://www.medworm.com/index.php?rid=2173580&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%3D19199871%26dopt%3DAbstract Authors: Stefani M, Liguri G The role of cholesterol as a susceptibility factor or a protective agent in neurodegeneration and, more generally, in amyloid-induced cytotoxicity is still controversial. Epidemiological studies on the hypercholesterolemia-AD risk relation and some reports indicating a beneficial effect of statin therapy suggest cholesterol as a susceptibility factor in AD. The ApoE4 genotype as a prevalent genetic risk factor for AD and the function of ApoE as main cholesterol carrier in the brain also underlie a close cholesterol load-AD risk relation. Finally, cell biology evidences support a critical involvement of lipid raft cholesterol in the modulation of beta- and gamma-secretase cleavage of APP with altered Abeta production. However, little exchange does exist betw... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173580 Sun, 01 Feb 2009 05:00:00 +0100 2173580 http://www.medworm.com/index.php?rid=2173579&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%3D19199872%26dopt%3DAbstract Authors: Wei H, Xie Z While anesthetics are indispensable clinical tools generally safe and effective, in some situations there is grown concern about selective neurotoxicity of these agents; the clinical significance is unclear as of yet. The mechanisms for inhalational anesthetics mediated cell damage are still not clear, although a role for calcium dysregulation has been suggested. For example, the inhaled anesthetic isoflurane decreases endoplasmic reticulum (ER) calcium concentration and increases that in the cytosol and mitochondria. Inhibition of ER calcium release, via either IP(3) or ryanodine receptors, significantly inhibited isoflurane neurotoxicity. Neurons made vulnerable to calcium dysregulation by overexpression of mutated presenilin-1 (PS1) or huntingtin (Q-111) protei... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173579 Sun, 01 Feb 2009 05:00:00 +0100 2173579 http://www.medworm.com/index.php?rid=2173578&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%3D19199873%26dopt%3DAbstract Authors: Coppedè F, Migliore L The vast majority of the studies performed so far and aimed at elucidating DNA repair mechanisms has been performed in mitotic cells, such as transformed or cancer cell lines. Therefore, our understanding of DNA repair mechanisms in post-mitotic cells, such as neurons, remains one of the most exciting areas for future investigations. Markers of DNA damage, particularly oxidative DNA damage, have been largely found in brain regions, peripheral tissues, and biological fluids of Alzheimer's disease (AD) patients. Moreover, recent studies from our and other groups in individuals affected by Mild Cognitive Impairment provided evidence that oxidative DNA damage is one of the earliest detectable events within the progression from a normal brain to dementia.... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173578 Sun, 01 Feb 2009 05:00:00 +0100 2173578 http://www.medworm.com/index.php?rid=2173577&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%3D19199874%26dopt%3DAbstract Conclusion: A direct IADL measure for dementia patients is able to detect small differences between MCI and NC and cross-sectionally and longitudinally, but does not distinguish between groups. PMID: 19199874 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173577 Sun, 01 Feb 2009 05:00:00 +0100 2173577 http://www.medworm.com/index.php?rid=2173576&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%3D19199875%26dopt%3DAbstract Authors: Weiner MF, Marquez de la Plata C, Fields BA, Womack KB, Rosenberg RN, Gong YH, Qu BX, Diaz-Arrastia R, Hynan LS We obtained brain MRIs, plasma homocysteine levels and apolipoprotein E genotyping for 11 American Indian Alzheimer disease (AD) subjects and 10 Indian controls. We calculated white matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV). There were no significant differences between AD subjects and controls in gender, history of hypertension, diabetes, or history of high cholesterol, but hypertension and diabetes were more common among AD subjects. There was no difference between AD and control groups in age (range for all subjects was 61-89 years), % Indian heritage, waist size ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173576 Sun, 01 Feb 2009 05:00:00 +0100 2173576 http://www.medworm.com/index.php?rid=2173575&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%3D19199876%26dopt%3DAbstract Authors: Wostyn P, Audenaert K, De Deyn PP Recent research findings provide evidence for Alzheimer's disease-related changes in brain diseases, such as normal pressure hydrocephalus and traumatic brain injury, and in glaucoma at the level of the retinal ganglion cells. This is a group of diseases that affect central nervous system tissue and are characterized by elevation of intracranial or intraocular pressure and/or local shear stress and strain. This strengthens the possibility that Alzheimer-type changes in these diseases may result at least in part from exposure of central nervous system tissue to elevated mechanical load. As activities or diseases with significant Valsalva effort can generate increased intracranial pressures, we hypothesize that individuals who frequently perform... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173575 Sun, 01 Feb 2009 05:00:00 +0100 2173575 http://www.medworm.com/index.php?rid=2173574&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%3D19199877%26dopt%3DAbstract Authors: Zach P, Kristofiková Z, Mrzílková J, Majer E, Selinger P, Spaniel F, Rípová D, Kenney J Investigations of alterations in brain asymmetry often focus on the planum temporale of patients with schizophrenia. Data also suggest changes in laterality of demented patients associated with a more marked impairment of the left hemisphere. Our study was performed on autoptic brain tissue of 84 patients, out of which there were 25 non-demented non-psychotic controls, 50 demented patients (34 Alzheimer disease, 9 multi - infarct dementia and 7 mixed-type dementia patients) and 9 people with schizophrenia. The plana temporalia were evaluated via a new volumetric method using dental resin matter. Areas, cortical thickness and volumes of the right and left planum temp... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173574 Sun, 01 Feb 2009 05:00:00 +0100 2173574 http://www.medworm.com/index.php?rid=2173573&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%3D19199878%26dopt%3DAbstract Authors: Schneider LS, Lahiri DK PMID: 19199878 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173573 Sun, 01 Feb 2009 05:00:00 +0100 2173573 http://www.medworm.com/index.php?rid=2173572&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%3D19199879%26dopt%3DAbstract Authors: Becker RE, Unni LK, Greig NH Commercial priorities have been identified as negative factors in drug development. We trace the problem to inattention to sound clinical pharmacology practices. When properly applied, clinical pharmacology and associated drug development sciences can, hand in hand, facilitate success in commercial drug development. PMID: 19199879 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173572 Sun, 01 Feb 2009 05:00:00 +0100 2173572 http://www.medworm.com/index.php?rid=2173571&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%3D19199880%26dopt%3DAbstract Authors: Castellani RJ, Perry G, Smith MA In a recent book, Dr. Peter Whitehouse describes Alzheimer's disease as a myth that cannot be separated from aging and, as such, the "disease" is simply an accelerated brain aging. While it is factually true that the aging brain and Alzheimer's disease are on a pathological continuum, this is true only in the most general sense - that is, the quantities of plaques and tangles in the brain. It is well known that standard pathological criteria do not address such factors as the nature and onset of clinical signs, kinetics of disease progression, and presence or absence of age-related co-morbidities such as hypertensive cerebrovascular disease and diabetes mellitus. Clearly, a 68 year old patient who dies of pneumonia while in a vegetative state a... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2173571 Sun, 01 Feb 2009 05:00:00 +0100 2173571 http://www.medworm.com/index.php?rid=2061825&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%3D19075587%26dopt%3DAbstract Authors: Cole NB A number of studies have demonstrated a role for transition metals and oxidative stress in the etiology of Parkinson's disease (PD). Genetic and biochemical evidence also clearly links the protein alpha-synuclein (alphaSyn) to PD and a number of associated diseases. In these "synucleinopathies", alphaSyn is deposited, often in oligomerized forms, as cytoplasmic inclusions known as Lewy bodies and Lewy neurites. alphaSyn cross-linking/oligomerization can occur via a number of processes, most stimulated by metal catalyzed oxidation (MCO). In PD, the increased sensitivity of midbrain neurons expressing high levels of oxidizable catecholamines may provide one clue to account for degeneration of these neurons. In other regions of the nervous system that develop Lewy body pa... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2061825 Mon, 01 Dec 2008 05:00:00 +0100 2061825 http://www.medworm.com/index.php?rid=2047948&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%3D19075575%26dopt%3DAbstract Authors: Zatta P PMID: 19075575 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047948 Mon, 01 Dec 2008 05:00:00 +0100 2047948 http://www.medworm.com/index.php?rid=2047947&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%3D19075576%26dopt%3DAbstract Authors: Drago D, Bolognin S, Zatta P Neurodegeneration is a complex and multifaceted process leading to many chronic diseased states. Neurodegenerative disorders include a number of different pathological conditions, like Alzheimer's and Parkinson's diseases, which share similar critical metabolic processes, such as protein aggregation, which could be affected by some metal ions. A huge number of reports indicate that, among putative aggravating factors, metal ions (Al, Zn, Cu, Fe) could specifically impair protein aggregation of Abeta, prion protein, ataxin, huntingtin, etc. and their oligomeric toxicity. While studying the molecular basis of these diseases, it has become clear that protein conformation plays a critical role in the pathogenic process. In this review, we will focus on... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047947 Mon, 01 Dec 2008 05:00:00 +0100 2047947 http://www.medworm.com/index.php?rid=2047946&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%3D19075577%26dopt%3DAbstract Authors: Morante S The aim of this review is to show how the challenging problem of understanding the physico-chemical basis of protein misfolding and aggregation which are at the origin of plaque formation in amyloid pathologies can be successfully investigated with a combination of modern spectroscopic techniques and advanced first principle numerical simulations. Within the vast group of diseases (more than 20) characterized by extra-cellular deposition of fibrillar material and generically called Amyloidosis, we shall focus on the Alzheimer's disease, a progressive and devastating neurodegenerative pathology affecting an important fraction of the world aged population. Well identified peptides (the so called Abeta-peptides) undergo a misfolding process during the development of the... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047946 Mon, 01 Dec 2008 05:00:00 +0100 2047946 http://www.medworm.com/index.php?rid=2047945&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%3D19075578%26dopt%3DAbstract Authors: Su B, Wang X, Nunomura A, Moreira PI, Lee HG, Perry G, Smith MA, Zhu X Multiple lines of evidence demonstrate that oxidative stress is an early event in Alzheimer's disease (AD), occurring prior to cytopathology, and therefore may play a key pathogenic role in AD. Oxidative stress not only temporally precedes the pathological lesions of the disease but also activates cell signaling pathways, which, in turn, contribute to lesion formation and, at the same time, provoke cellular responses such as compensatory upregulation of antioxidant enzymes found in vulnerable neurons in AD. In this review, we provide an overview of the evidence of oxidative stress and compensatory responses that occur in AD, particularly focused on potential sources of oxidative stress and the roles and mec... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047945 Mon, 01 Dec 2008 05:00:00 +0100 2047945 http://www.medworm.com/index.php?rid=2047944&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%3D19075579%26dopt%3DAbstract Authors: Naylor R, Hill AF, Barnham KJ Alzheimer's disease (AD) is the most common form of dementia in the elderly, and is characterized by the deposition of extracellular amyloid plaques primarily composed of the beta-amyloid peptide (Abeta). While these plaques define the pathology of AD, disease progression has been shown to correlate more closely with the level of synaptotoxicity induced by soluble Abeta oligomers. Recent evidence suggests that these oligomers are covalently crosslinked, possibly due to the interaction of Abeta with redox-active metal ions. These findings offer new avenues for the treatment and prevention of disease, by modulating metal binding or preventing the formation of neurotoxic Abeta oligomers. An understanding of the chemical nature of Abeta is also requir... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047944 Mon, 01 Dec 2008 05:00:00 +0100 2047944 http://www.medworm.com/index.php?rid=2047943&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%3D19075580%26dopt%3DAbstract Authors: Takano K Amyloid beta peptide (Abeta), 42-residue peptide and its variations, is known to form amyloid fibrils in Alzheimer's disease. Solid-state NMR study reveals a parallel beta-sheet structure in the Abeta fibrils. The atomic level structure of Abeta in aqueous environment, however, has not been determined, because of its tendency to aggregate. There are several reports that soluble forms of Abeta possess intrinsic neurotoxicity. It has recently become possible to determine the crystal structure of Abeta fragments in an aqueous solution without organic solvents and detergents using a fusion technique with a hyperthermophile protein. Abeta (28-42) forms a beta-conformation. This fusion technique enables us to obtain structural information at atomic resolution for amyloidoge... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047943 Mon, 01 Dec 2008 05:00:00 +0100 2047943 http://www.medworm.com/index.php?rid=2047942&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%3D19075581%26dopt%3DAbstract Authors: Yan Y, Wang C It is widely accepted that Abeta42 aggregation is a central event in the pathogenesis of Alzheimer's disease. Abeta42 oligomers and fibrils cause the breakdown of neural circuits, neuronal death and eventually dementia. There are a number of physiological molecules that can protect Abeta42 from aggregation. Promoting such protective molecules and mechanisms against Abeta42 aggregation may be a novel direction in AD drug discovery. One of the most striking protective molecules is none other than Abeta40, which inhibits Abeta42 aggregation in a specific and dosage dependent manner. Abeta40 is a critical, built-in mechanism against Abeta42 aggregation. A number of other molecules and mechanisms also inhibit Abeta42 aggregation, such as heat shock proteins, L-PGDS, h... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047942 Mon, 01 Dec 2008 05:00:00 +0100 2047942 http://www.medworm.com/index.php?rid=2047941&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%3D19075582%26dopt%3DAbstract Authors: Ohyagi Y The amyloid cascade hypothesis is well known hypothesis describing the pathogenesis of Alzheimer's disease (AD). On the basis of this hypothesis, inhibition of amyloid beta-protein (Abeta) generation and aggregation, enhancement of extracellular Abeta removal, and Abeta vaccination are currently under investigation. Intracellular Abeta may be even more important than extracellular Abeta, since intraneuronal Abeta accumulation commonly precedes extracellular Abeta deposition in several familial AD-related mutant presenilin 1-transgenic mice. Various pathogenic mechanisms involving intracellular Abeta such as mitochondrial toxicity, proteasome impairment and synaptic damage have been suggested. Recently, we have reported that cytosolic Abeta42 accumulation leads to p53 ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047941 Mon, 01 Dec 2008 05:00:00 +0100 2047941 http://www.medworm.com/index.php?rid=2047940&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%3D19075583%26dopt%3DAbstract Authors: Müller T, Jung K, Ullrich A, Schrötter A, Meyer HE, Stephan C, Egensperger R, Marcus K Human post-mortem brain samples are excellent source material for the analysis of age-related disorders such as Alzheimer's disease (AD). Moreover, data obtained from cell culture- or mouse model-related experiments often need to be validated by using human tissue. In a variety of studies over the last few years, a huge list of genes or proteins with differential expression or abundance between AD-related and control tissue has been reported. However, highly important issues such as changes in post-mortem time, sex, age etc. of the patients have been rarely included in the analysis. In our study we examined human frontal brain samples of 10 AD patients vs. 10 unaffected controls us... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047940 Mon, 01 Dec 2008 05:00:00 +0100 2047940 http://www.medworm.com/index.php?rid=2047939&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%3D19075584%26dopt%3DAbstract Authors: Rezaei H The PrP propensity to adopt different structures is tightly linked to transmissible spongiform encephalopathies (TSE) which include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scjeinker (GSS) and Kuru syndrome. In most cases, TSE is associated with the accumulation in the brain of an abnormally folded protease-resistant protein, PrP(Sc) or PrPres, which is derived from a cellular host-encoded protease-sensitive conformer, designated PrP(C). The prion propagation in the brain is postulated to occur via a conformational change of PrP(C) into the amyloidogenic form PrP(Sc), characterized by a high beta sheet content. The characterization of PrP(SC) oligomers as well as their biological activity is currently an area of active research. Indeed, PrP(Sc) struc... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047939 Mon, 01 Dec 2008 05:00:00 +0100 2047939 http://www.medworm.com/index.php?rid=2047938&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%3D19075585%26dopt%3DAbstract Authors: Mendola DL, Pietropaolo A, Pappalardo G, Zannoni C, Rizzarelli E Prion diseases are fatal neurodegenerative disorders related to the conformational alteration of the prion protein (PrP(C)) into a pathogenic and protease-resistant isoform PrP(Sc). PrP(C) is a cell surface glycoprotein expressed mainly in the central nervous system and despite numerous efforts to elucidate its physiological role, the exact biological function remains unknown. Many lines of evidences indicate that prion is a copper binding protein and thus involved in the copper metabolism. Prion protein is not expressed only in mammals but also in other species such as birds, reptiles and fishes. However, it is noteworthy to point out that prion diseases are only observed in mammals while they seem to be spared ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047938 Mon, 01 Dec 2008 05:00:00 +0100 2047938 http://www.medworm.com/index.php?rid=2047937&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%3D19075586%26dopt%3DAbstract Authors: Sahara N, Maeda S, Takashima A Intracellular accumulation of filamentous tau proteins is a defining feature of neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and frontotemporal dementia with Parkinsonism linked to chromosome 17, all known collectively as tauopathies. Tau protein is a member of microtubule (MT)-associated proteins. Tau is a highly soluble and natively unfolded protein dominated by a random coil structure in solution. It is believed that aberrant modifications of tau, including phosphorylation, truncation, and conformational changes, induce filamentous aggregation. However, the mechanism underlying the conversion of tau protein from a soluble state to one of insoluble aggregat... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047937 Mon, 01 Dec 2008 05:00:00 +0100 2047937 http://www.medworm.com/index.php?rid=2047936&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%3D19075587%26dopt%3DAbstract Authors: Cole NB A number of studies have demonstrated a role for transition metals and oxidative stress in the etiology of Parkinson's disease (PD). Genetic and biochemical evidence also clearly links the protein alpha-synuclein (alphaSyn) to PD and a number of associated diseases. In these "synucleinopathies", (alphaSyn is deposited, often in oligomerized forms, as cytoplasmic inclusions known as Lewy bodies and Lewy neurites. (alphaSyn cross-linking/oligomerization can occur via a number of processes, most stimulated by metal catalyzed oxidation (MCO). In PD, the increased sensitivity of midbrain neurons expressing high levels of oxidizable catecholamines may provide one clue to account for degeneration of these neurons. In other regions of the nervous system that develop Lewy body ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=2047936 Mon, 01 Dec 2008 05:00:00 +0100 2047936 http://www.medworm.com/index.php?rid=1886854&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%3D18855588%26dopt%3DAbstract Authors: Chafekar SM, Zwart R, Veerhuis R, Vanderstichele H, Baas F, Scheper W Alzheimer's disease (AD) is characterized by the aggregation and subsequent deposition of misfolded beta-amyloid (Abeta) peptide. The unfolded protein response (UPR) is activated by misfolded protein stress in the endoplasmic reticulum (ER). In previous studies we demonstrated mild activation of the UPR by extracellularly applied oligomeric but not fibrillar Abeta1-42. In addition, we showed that oligomeric Abeta1-42 is internalized by cells, whereas fibrillar Abeta1-42 remains on the outside of the cell. Inhibition of Abeta uptake specifically inhibits toxicity of Abeta1-42 oligomers, underscoring the toxic potential of intracellular Abeta. Therefore, in the present study, we investigated the connection bet... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1886854 Wed, 01 Oct 2008 04:00:00 +0100 1886854 http://www.medworm.com/index.php?rid=1886853&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%3D18855589%26dopt%3DAbstract Authors: McLarnon JG, Ryu JK Injection of amyloid-beta peptide (Abeta1-42) into hippocampal and cortical regions of brain may have utility as an animal model of Alzheimer's disease (AD) emphasizing the inflammatory component of disease pathology. This review summarizes recent evidence supporting the relevance of the peptide injection model to describe inflammatory conditions in AD brain. A wide spectrum of responses are considered from effects of Abeta1-42 on animal behavior and cognitive performance to peptide actions at the cellular and molecular levels. In the latter case a particular focus is placed on inflammatory responses mediated by activated microglia. Specific pharmacological modulations of microglial signaling pathways and factors and how they shape patterns of inflammatory ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1886853 Wed, 01 Oct 2008 04:00:00 +0100 1886853 http://www.medworm.com/index.php?rid=1880393&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%3D18855583%26dopt%3DAbstract Authors: Pomponi M, Di Gioia A, Bria P, Pomponi MF Alzheimer's disease (AD) leads to a dramatic decline in cognitive abilities and memory. A more modest disruption of memory often occurs in normal aging and the same circuits that are devastated through degeneration in AD are vulnerable to sub-lethal age-related changes that alter synaptic transmission. There are numerous indications that aberrant plasticity is critically involved in Alzheimer's. Is ageing itself the major risk factor for AD? Is AD an acceleration of normal ageing? We assume that the ability of the brain is to modify its own structural organization and functioning which is liable to become impaired in ageing until it becomes dramatically impaired in Alzheimer's. Moreover, ageing can compromise the conversion of dietary ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1880393 Wed, 01 Oct 2008 04:00:00 +0100 1880393 http://www.medworm.com/index.php?rid=1880392&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%3D18855584%26dopt%3DAbstract Authors: Jeynes B, Provias J There is significant evidence to suggest that a damaged or dysfunctional blood-brain barrier (BBB) may contribute to the pathogenesis of Alzheimer's disease (AD) lesions. Lipoprotein receptor-related protein (LRP-1) and receptor for advanced glycation end products (RAGE) are known to be important (BBB) capillary transport proteins. Altered expression of either of these capillary endothelial LRP-1 and RAGE receptor proteins could indicate a dysfunction of the BBB and its transport regulation of beta-amyloid (Abeta). Cortical samples from the superior temporal (ST) and calcarine occipital (COC) cortices of ten confirmed AD brains and ten comparison group (CG) brains were examined. The densities of neurofibrillary tangles (NFTs), senile plaques (SPs) and LRP-1... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1880392 Wed, 01 Oct 2008 04:00:00 +0100 1880392 http://www.medworm.com/index.php?rid=1880391&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%3D18855585%26dopt%3DAbstract Insulin resistance and Alzheimer's disease: molecular links & clinical implications. Curr Alzheimer Res. 2008 Oct;5(5):438-47 Authors: Neumann KF, Rojo L, Navarrete LP, Farías G, Reyes P, Maccioni RB Hyperinsulinemia as well as type II diabetes mellitus are among the risk factors for Alzheimer's disease (AD). However, the molecular and cellular basis that link insulin resistance disorders and diabetes with AD are far from clear. Here, we discuss the potential molecular mechanisms that may explain the participation of these metabolic disorders in the pathogenesis of AD. The human brain uses glucose as a primary fuel; insulin secreted by the pancreas cross the blood-brain barrier (BBB), reaching neurons and glial cells, and exerts a region-specific effect on glucose meta... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1880391 Wed, 01 Oct 2008 04:00:00 +0100 1880391 http://www.medworm.com/index.php?rid=1880390&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%3D18855586%26dopt%3DAbstract Authors: Davis W Cholesterol transport is a key regulator of amyloid precursor protein (APP) processing and beta-amyloid (Abeta production, implicated in Alzheimer's disease. Perturbation of cholesterol transport can be pharmacologically induced by the class II amphiphile 3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one, U18666a; however, the mechanisms by which U18666a controls APP metabolism and trafficking have not been elucidated. We proposed to determine how U18666a regulates APP holoprotein metabolism and trafficking in N2a mouse neuroblastoma cells stably expressing the human APP protein. Secretion of Abeta1-40 was reduced in U18666a-treated cells. U18666a elevated the steady state level of the APP holoprotein but not APP mRNA levels. U18666a increased sAPPalpha secretion and ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1880390 Wed, 01 Oct 2008 04:00:00 +0100 1880390 http://www.medworm.com/index.php?rid=1880389&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%3D18855587%26dopt%3DAbstract Authors: Mancuso M, Orsucci D, Siciliano G, Murri L To date, the beta amyloid (Abeta) cascade hypothesis remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is unclear. The mitochondria play central role in the bioenergetics of the cell and apoptotic cell death. In the past 20 years research has been directed at clarifying the involvement of mitochondria and defects in mitochondrial oxidative phosphorylation in late-onset neurodegenerative disorders, including AD. Morphological, biochemical and genetic abnormalities of the mitochondria in several AD tissues have been reported. Impaired mitochondrial respiration, particularly COX deficiency, has been observed in brain, platelets and fibroblasts of AD patients. The "mitochond... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1880389 Wed, 01 Oct 2008 04:00:00 +0100 1880389 http://www.medworm.com/index.php?rid=1880388&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%3D18855588%26dopt%3DAbstract Authors: Chafekar SM, Zwart R, Veerhuis R, Vanderstichele H, Baas F, Scheper W Alzheimer's disease (AD) is characterized by the aggregation and subsequent deposition of misfolded beta-amyloid (Abeta) peptide. The unfolded protein response (UPR) is activated by misfolded protein stress in the endoplasmic reticulum (ER). In previous studies we demonstrated mild activation of the UPR by extracellularly applied oligomeric but not fibrillar Abeta(1-42). In addition, we showed that oligomeric Abeta(1-42) is internalized by cells, whereas fibrillar Abeta(1-42) remains on the outside of the cell. Inhibition of Abeta uptake specifically inhibits toxicity of Abeta(1-42) oligomers, underscoring the toxic potential of intracellular Abeta. Therefore, in the present study, we investigated the connec... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1880388 Wed, 01 Oct 2008 04:00:00 +0100 1880388 http://www.medworm.com/index.php?rid=1880387&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%3D18855589%26dopt%3DAbstract Authors: McLarnon JG, Ryu JK Injection of amyloid-beta peptide (Abeta(1-42)) into hippocampal and cortical regions of brain may have utility as an animal model of Alzheimer's disease (AD) emphasizing the inflammatory component of disease pathology. This review summarizes recent evidence supporting the relevance of the peptide injection model to describe inflammatory conditions in AD brain. A wide spectrum of responses are considered from effects of Abeta(1-42) on animal behavior and cognitive performance to peptide actions at the cellular and molecular levels. In the latter case a particular focus is placed on inflammatory responses mediated by activated microglia. Specific pharmacological modulations of microglial signaling pathways and factors and how they shape patterns of inflammat... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1880387 Wed, 01 Oct 2008 04:00:00 +0100 1880387 http://www.medworm.com/index.php?rid=1880386&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%3D18855590%26dopt%3DAbstract This article presents a new paradigm of Artificial Neural Networks (ANNs): the Auto-Contractive Maps (Auto-CM). The Auto-CM differ from the traditional ANNs under many viewpoints: the Auto-CM start their learning task without a random initialization of their weights, they meet their convergence criterion when all their output nodes become null, their weights matrix develops a data driven warping of the original Euclidean space, they show suitable topological properties, etc. Further two new algorithms, theoretically linked to Auto-CM are presented: the first one is useful to evaluate the complexity and the topological information of any kind of connected graph: the H Function is the index to measure the global hubness of the graph generated by the Auto-CM weights matrix. The second one is ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1880386 Wed, 01 Oct 2008 04:00:00 +0100 1880386 http://www.medworm.com/index.php?rid=1701577&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%3D18690831%26dopt%3DAbstract Authors: Barry G, Ross IL A reduction of neurosteroids in the brain may initiate sporadic Alzheimer's disease (AD) which comprises >99% of all AD cases. AD research is currently focused on aberrant amyloid precursor protein (APP) processing and the hyper-phosphorylation of tau protein. This is based on early-onset genetic and pathological observations clearly showing that these markers are involved in the progression of the disease. However, there is still ongoing debate as to the key pathological events in the sporadic form of AD where the Abeta and tau genes are not usually mutated. The vulnerability of the transentorhinal cortex, which displays the first architectural signs of AD, may be related to its role as the entry point for an enormous amount of excitatory information, the ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701577 Fri, 01 Aug 2008 04:00:00 +0100 1701577 http://www.medworm.com/index.php?rid=1701576&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%3D18690832%26dopt%3DAbstract Authors: Becker RE, Greig NH Recently, a number of Alzheimer's disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of resea... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701576 Fri, 01 Aug 2008 04:00:00 +0100 1701576 http://www.medworm.com/index.php?rid=1701575&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%3D18690833%26dopt%3DAbstract Authors: Kassner SS, Bonaterra GA, Kaiser E, Hildebrandt W, Metz J, Schröder J, Kinscherf R Almost 2% of the population of western industrialized countries are affected by Alzheimer's disease (AD). Nevertheless the pathogenetic process leading to this neurodegenerative disease is widely unknown. Thus, we focus on novel pathophysiological aspects of AD. We hypothesize that AD patients reveal increased levels of peripheral blood mononuclear cells (PBMCs) expressing proinflammatory (COX-2, TNF-alpha, CD40), proapoptotic (PARP-1), adhesion-relevant (CD38) or AD associated (C99, BACE1, Presenilin-1) proteins as well as elevated proinflammatory biochemical plasma parameters. Therefore, PBMCs of AD patients and age-matched control subjects were studied by two color fluorescence-activated... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701575 Fri, 01 Aug 2008 04:00:00 +0100 1701575 http://www.medworm.com/index.php?rid=1701574&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%3D18690834%26dopt%3DAbstract We describe and analyze important posttranslational modifications: hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and truncation. We discuss how these post-translational modifications can alter tau's biological function and what is known about tau self-assembly, and we propose a mechanism of tau polymerization. We analyze the impact of natural mutations on tau that cause fronto-temporal dementia associated with chromosome 17 (FTDP-1 7). Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and we propose a mechanism of neurodegeneration. PMID: 18690834 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701574 Fri, 01 Aug 2008 04:00:00 +0100 1701574 http://www.medworm.com/index.php?rid=1701573&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%3D18690835%26dopt%3DAbstract In this study, we examined the relationship between one type of prefrontal-dependent executive function, discrimination reversal-learning, and levels of the amyloid beta protein (Abeta) of 40 and 42 residues in a transgenic mouse model (Tg2576) of the over-expression of the familial AD mutant form of the amyloid precursor protein (APPsw). Tg2576 and their non-transgenic (NTg) littermates were assessed at 3 and 6 months of age when there is little to no amyloid plaque deposition. After reversal-learning assessment, Abeta40 and Abeta42 were quantified in the prefrontal cortex and hippocampus. Tg2576 mice were impaired in reversal-learning at 6 but not 3 months of age when compared to the NTg group. Coincidently, there was a corresponding approximately 3-fold increase of Abeta42 levels in the... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701573 Fri, 01 Aug 2008 04:00:00 +0100 1701573 http://www.medworm.com/index.php?rid=1701572&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%3D18690836%26dopt%3DAbstract The objective of this study is to use laser-induced fluorescence spectroscopy to compare structural (collagen content) and functional (apoptosis) parameters in brain tissues and isolated vessels of AD patients to age-matched controls. Our results show significantly higher fluorescent labeling for apoptosis in AD vessels compared to controls. Also, there is significantly higher autofluorescence (reflecting levels of collagen and other proteins that autofluoresce) in AD brain and vessels compared to controls. Western blot analysis of collagen subtypes shows elevated type I and type III and reduced type IV levels in AD vessels. These data demonstrate that changes in the amount and type of collagen occur in AD brain and suggest that cerebral vessel injury is part of AD pathology. PMID: 186... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701572 Fri, 01 Aug 2008 04:00:00 +0100 1701572 http://www.medworm.com/index.php?rid=1701571&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%3D18690837%26dopt%3DAbstract Authors: Pahnke J, Wolkenhauer O, Krohn M, Walker LC In recent years it has become evident that ABC transporters fulfill important barrier functions in normal organs and during disease processes. Most importantly, resistance to drugs in cancer cells led to intense oncological and pharmacological investigations in which researchers were able to highlight important pharmacological interactions of chemotherapeuticals with ABC transporter function. Recently, the development of neurodegenerative diseases and the maintenance of neuronal stem cells have been linked to the activity of ABC transporters. Here, we summarize findings from cell culture experiments, animal models and studies of patients with Alzheimer's disease. Furthermore, we discuss pharmacological interactions and computational ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701571 Fri, 01 Aug 2008 04:00:00 +0100 1701571 http://www.medworm.com/index.php?rid=1701570&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%3D18690838%26dopt%3DAbstract This study will enable us to evaluate the efficacy of EGb761 in the prevention of AD, and to assess the usefulness of various baseline characteristics as predictors of conversion to AD in this population. PMID: 18690838 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701570 Fri, 01 Aug 2008 04:00:00 +0100 1701570 http://www.medworm.com/index.php?rid=1701569&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%3D18690839%26dopt%3DAbstract Authors: Sparks DL, Kryscio RJ, Sabbagh MN, Connor DJ, Sparks LM, Liebsack C Statins have been reported to reduce the risk and be of benefit in the treatment of Alzheimer's disease (AD). Individuals enrolling in the randomized controlled trial testing two anti-inflammatory agents for primary prevention of AD (Alzheimer's Disease Anti-inflammatory Prevention Trial; ADAPT) were allowed the elective use of statins. Our objective was to assess whether statin use is associated with reduced risk of incident AD among ADAPT participants. In primary ADAPT study , participants were assessed annually for cholesterol levels and cognitive status. If impairment in cognition was noted, a dementia evaluation was performed. Onset of mild cognitive impairment (MCI) or AD was taken as the date of this ev... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1701569 Fri, 01 Aug 2008 04:00:00 +0100 1701569 http://www.medworm.com/index.php?rid=1509419&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%3D18537539%26dopt%3DAbstract Authors: Soreq H, Gazit E PMID: 18537539 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509419 Sun, 01 Jun 2008 04:00:00 +0100 1509419 http://www.medworm.com/index.php?rid=1509418&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%3D18537540%26dopt%3DAbstract Authors: Cerpa W, Dinamarca MC, Inestrosa NC Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the growing population of elderly people. A characteristic of AD is the accumulation of plaques in the brain of AD patients, and theses plaques mainly consist of aggregates of amyloid beta-peptide (Abeta). All converging lines of evidence suggest that progressive accumulation of the Abeta plays a central role in the genesis of Alzheimer's disease and it was long understood that Abeta had to be assembled into extracellular amyloid fibrils to exert its cytotoxic effects. This process could be modulated by molecular chaperones which inhibit or accelerate the amyloid formation. The enzyme Acetylcholinesterase (AChE) induces Abeta fibrils formation, forming a stable compl... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509418 Sun, 01 Jun 2008 04:00:00 +0100 1509418 http://www.medworm.com/index.php?rid=1509417&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%3D18537541%26dopt%3DAbstract In this study, we review our current understanding of the computer-predicted conformations of amino acids 23-28 in the monomer of Abeta(21-30) and the monomers Abeta40 and Abeta42. On the basis of new simulations on dimers of full-length Abeta, we propose that the rate-limiting step involves the formation of a multimeric beta-sheet spanning the central hydrophobic core (residues 17-21). PMID: 18537541 [PubMed - in process] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509417 Sun, 01 Jun 2008 04:00:00 +0100 1509417 http://www.medworm.com/index.php?rid=1509416&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%3D18537542%26dopt%3DAbstract Authors: Bousset L, Savistchenko J, Melki R The proteins Ure2, Sup35 and Rnq1 from the baker's yeast have infectious properties, termed prions, at the origin of heritable and transmissible phenotypic changes. It is widely believed that prion properties arise from the assembly of Ure2p, Sup35p and Rnq1p into insoluble fibrils. Yeast prions possess regions crucial for their propagation that can be either N- or C-terminal. These regions have unusual amino acid composition. They are very rich in glutamine and asparagine residues and resemble in that to huntingtin, a protein involved in the neurodegenerative Huntington's disease. Yeast prions assembly process has been hypothesized to be the consequence of the properties of glutamines and asparagines to engage in polar protein-protein intera... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509416 Sun, 01 Jun 2008 04:00:00 +0100 1509416 http://www.medworm.com/index.php?rid=1509415&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%3D18537543%26dopt%3DAbstract Authors: Uversky VN Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found during the equilibrium and kinetic (un)folding studies of several globular proteins and later described as one of the structural forms of natively unfolded proteins. The flexibility of this structural form is essential for the conformational rearrangements driving the formation of the core cross-beta structure of the amyloid fibril. Obviously, molecular mec... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509415 Sun, 01 Jun 2008 04:00:00 +0100 1509415 http://www.medworm.com/index.php?rid=1509414&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%3D18537544%26dopt%3DAbstract We report here the application of fiber x-ray diffraction to monitor these structural indicators of amyloid fiber assembly in the presence of small, aromatic molecules, some of which have been assessed by other techniques as being inhibitory. The compounds included butylated hydroxytoluene, chloramphenicol, cotinine, curcumin, diphenylalanine (FF), ethyl 3-aminobenzoate methane sulfonate, hexachlorophene, melatonin, methylpyrrolidine, morin, nicotine, phenolphthalaine, PTI-00703((R)) (Cat's claw), pyridine, quinine, sulfadiazine, tannic acid, tetracaine, tetrachlorosalicylanilide, and tetracycline. Their effects on the aggregation of Abeta1-40, Abeta11-25, Abeta12-28, Abeta17-28, Abeta16-22, and Abeta16-22[methylated] analogues were characterized in terms of the integral widths and integra... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509414 Sun, 01 Jun 2008 04:00:00 +0100 1509414 http://www.medworm.com/index.php?rid=1509413&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%3D18537545%26dopt%3DAbstract Authors: Baxa U Amyloid fibrils are elongated protein aggregates well known for their association with many human diseases. However, similar structures have also been found in other organisms and amyloid fibrils can also be formed in vitro by other proteins usually under non-physiological conditions. In all cases, these fibrils assemble in a nucleated polymerization reaction with a pronounced lag phase that can be eliminated by supplying pre-formed fibrils as seeds. Once formed, the fibrils are usually very stable, except for their tendency to break into smaller pieces forming more growing ends in the process. These properties give amyloid fibers a self-replicating character dependent only on a source of soluble protein. For some systems and under certain circumstances this can lead to... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509413 Sun, 01 Jun 2008 04:00:00 +0100 1509413 http://www.medworm.com/index.php?rid=1509412&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%3D18537546%26dopt%3DAbstract Authors: Rahimi F, Shanmugam A, Bitan G Several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases, are characterized pathognomonically by the presence of intra- and/or extracellular lesions containing proteinaceous aggregates, and by extensive neuronal loss in selective brain regions. Related non-neuropathic systemic diseases, e.g., light-chain and senile systemic amyloidoses, and other organ-specific diseases, such as dialysis-related amyloidosis and type-2 diabetes mellitus, also are characterized by deposition of aberrantly folded, insoluble proteins. It is debated whether the hallmark pathologic lesions are causative. Substantial evidence suggests that these aggregates are the end state of aberrant protein folding whereas the actual cul... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509412 Sun, 01 Jun 2008 04:00:00 +0100 1509412 http://www.medworm.com/index.php?rid=1509411&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%3D18537547%26dopt%3DAbstract Authors: Weinshenker D Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients, and its prevalence is expected to soar in coming decades. Neuropathologically, AD is characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, and cholinergic neuronal loss. In addition to the hallmark of memory loss, the disease is associated with other neuropsychiatric and behavioral abnormalities, including psychosis, aggression, and depression. Although cholinergic cell loss is clearly an important attribute of the pathological process, another well-described yet underappreciated early feature of AD pathogenesis is degeneration of the locus coeruleus (LC), which serves as the main source of norepinephrine (NE) supplying various cortical... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1509411 Sun, 01 Jun 2008 04:00:00 +0100 1509411 http://www.medworm.com/index.php?rid=1482590&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%3D18393794%26dopt%3DAbstract Authors: Checler F PMID: 18393794 [PubMed - indexed for MEDLINE] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482590 Tue, 01 Apr 2008 04:00:00 +0100 1482590 http://www.medworm.com/index.php?rid=1482589&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%3D18393795%26dopt%3DAbstract Authors: Nathalie P, Jean-Noël O Alzheimer's disease is characterized by the presence of two types of lesions in brain: neurofibrillary tangles and senile plaques. Intraneuronal neurofibrillary tangles are made of paired helical filaments containing hyperphosphorylated microtubule associated protein tau. Extracellular senile plaques contain a core of beta-amyloid peptide (Abeta), which is produced by cleavage of the Amyloid Precursor Protein (APP). Among the two catabolic pathways of APP, the amyloidogenic pathway producing Abeta peptides was intensively studied in different cellular models expressing human APP. Differences in APP processing and in toxicity resulting from Abeta accumulation can be observed from one cell type to another. In particular, primary cultures of neurons p... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482589 Tue, 01 Apr 2008 04:00:00 +0100 1482589 http://www.medworm.com/index.php?rid=1482588&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%3D18393796%26dopt%3DAbstract Authors: Cole SL, Vassar R Amyloid plaques, hallmark neuropathological lesions in Alzheimer's disease (AD) brain, are composed of the beta-amyloid peptide (Abeta). Much evidence suggests that Abeta is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. Given the strong correlation between Abeta and AD, therapeutic strategies to lower cerebral Abeta levels should prove beneficial for AD treatment. Abeta is derived from amyloid precursor protein (APP) via cleavage by two proteases, beta- and gamma-secretase. The beta-secretase has been identified as a novel aspartic protease named BACE1 (beta-site APP Cleaving Enzyme 1) that initiates Abeta formation. Importantly, BACE1 appears to be dysregulated in AD. As the rate-limi... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482588 Tue, 01 Apr 2008 04:00:00 +0100 1482588 http://www.medworm.com/index.php?rid=1482587&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%3D18393797%26dopt%3DAbstract Authors: Ghosh AK, Kumaragurubaran N, Hong L, Koelsh G, Tang J Memapsin 2 (beta-secretase, BACE 1) processing of beta-amyloid precursor protein is the first step in the pathway leading to the production of amyloid-beta, thus, it is a major target for the development of inhibitor drug for the treatment of Alzheimers's Disease. Although there are distinctive advantages of this protease as a drug target, the development of drug-like memapsin 2 inhibitors has been somewhat slow since the cloning of the protease seven years ago. Here we review the progress of memapsin 2 inhibitor development using crystal structure-based design cycles. Recent progress has evolved the inhibitors into sizes sufficiently small to penetrate cell membranes and the blood-brain barrier yet retain potency for the i... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482587 Tue, 01 Apr 2008 04:00:00 +0100 1482587 http://www.medworm.com/index.php?rid=1482586&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%3D18393798%26dopt%3DAbstract Authors: Dries DR, Yu G In this review, we discuss the biology of gamma-secretase, an enigmatic enzyme complex that is responsible for the generation of the amyloid-beta peptide that constitutes the amyloid plaques of Alzheimer's disease. We begin with a brief review on the processing of the amyloid precursor protein and a brief discussion on the family of enzymes involved in regulated intramembrane proteolysis, of which gamma-secretase is a member. We then identify the four major components of the gamma-secretase complex - presenilin, nicastrin, Aph-1, and Pen-2 - with a focus on the identification of each and the role that each plays in the maturation and activity of the complex. We also discuss two new proteins that may play a role in modulating the assembly and activity of the gamm... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482586 Tue, 01 Apr 2008 04:00:00 +0100 1482586 http://www.medworm.com/index.php?rid=1482585&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%3D18393799%26dopt%3DAbstract Authors: Steiner H Mutations in the presenilin 1 (PS1) gene are the major cause of familial Alzheimer s disease (AD). They effect an increased production of the highly neurotoxic 42 amino acid variant of the amyloid-beta peptide (Abeta), which is believed to initiate the disease. Abeta is the product of two consecutive cleavages of the beta-amyloid precursor protein (APP) by two proteases, beta-secretase and gamma-secretase. The latter enzyme has been identified as an intramembrane-cleaving multiprotein complex that apart from APP cleaves a large number of other type I transmembrane proteins. PS1 and its homologue PS2 are essential for gamma-secretase cleavage and more than a decade after their discovery it is now firmly established that they function as catalytic subunits of gamma-sec... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482585 Tue, 01 Apr 2008 04:00:00 +0100 1482585 http://www.medworm.com/index.php?rid=1482584&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%3D18393800%26dopt%3DAbstract Authors: Wolfe MS Gamma-secretase is a multi-protein complex that proteolyzes the transmembrane region of the amyloid beta-peptide (Abeta) precursor (APP), producing the Abeta peptide implicated in the pathogenesis of Alzheimer's disease (AD). This protease has been a top target for AD, and various inhibitors have been identified, including transition-state analogue inhibitors that interact with the active site, helical peptides that interact with the initial substrate docking site, and other less peptide-like, more drug-like compounds. Although one gamma-secretase inhibitor has advanced into late-phase clinical trials, concerns about inhibiting this protease remain. The protease complex cleaves a number of other substrates, and in vivo toxicities observed with gamma-secretase inhibito... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482584 Tue, 01 Apr 2008 04:00:00 +0100 1482584 http://www.medworm.com/index.php?rid=1482583&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%3D18393801%26dopt%3DAbstract Authors: Kametani F The accumulation and deposition of fibrillar Abeta is thought the primary cause of Alzheimer's disease (AD). Abeta is generated by sequential proteolytic processing involving beta- and gamma-secretase on Amyloid beta protein precursor (APP). Recently, gamma-secretase was shown to cleave near the cytoplasmic membrane boundary of APP, called epsilon-site cleavage, as well as in the middle of the membrane domain, called gamma-site cleavage. Recent findings indicate that gamma- and epsilon-site cleavage are regulated independently. In this review, the reduction of epsilon-site cleavage in AD and the importance of epsilon-site cleavage are discussed. PMID: 18393801 [PubMed - indexed for MEDLINE] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482583 Tue, 01 Apr 2008 04:00:00 +0100 1482583 http://www.medworm.com/index.php?rid=1482582&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%3D18393802%26dopt%3DAbstract Authors: Xia W Mutations in two genes, presenilin 1 (PS1) and its homologue presenilin 2 (PS2), account for a majority of early onset familial Alzheimer disease cases which are characterized by intracellular neurofibrillary tangles and extracellular amyloid fibrils composed of the amyloid beta protein (Abeta). Abeta is derived from sequential cleavages of Amyloid Precursor Protein (APP) by beta-secretase and gamma-secretase, the latter is composed of four components, PS1, nicastrin (NCT), presenilin enhancer 2 (PEN-2), and anterior pharynx defective (APH-1). These components not only maintain the stability of the gamma-secretase complex but also regulate the activity of presenilinase, the protease responsible for the cleavage of full length PS1 into N-terminal and C-terminal fragments ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482582 Tue, 01 Apr 2008 04:00:00 +0100 1482582 http://www.medworm.com/index.php?rid=1482581&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%3D18393803%26dopt%3DAbstract Authors: Postina R Accumulation of amyloid beta-peptides (Abeta) in the brain is believed to contribute to the development of Alzheimer disease (AD). Abeta, a 40-42 amino acid-comprising proteolytical fragment of the amyloid precursor protein (APP), is released from APP by sequential cleavages via beta- and gamma-secretases. However, the predominant route of APP processing consists of successive cleavages by alpha- and gamma-secretases. Alpha-secretase attacks APP inside the Abeta sequence, and therefore prevents formation of neurotoxic Abeta. After cleavage by alpha-secretase, the soluble N-terminal domain of APP, which possesses neurotrophic and neuroprotective properties, is released. In AD patients, a decrease in alpha-secretase processing of APP has been found and therefore, strat... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482581 Tue, 01 Apr 2008 04:00:00 +0100 1482581 http://www.medworm.com/index.php?rid=1482580&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%3D18393804%26dopt%3DAbstract Authors: Deuss M, Reiss K, Hartmann D Disintegrin metalloproteases of the ADAM family form a large (at present > 40 members in mammals) family of multidomain membrane proteins that in their ectodomain combine a cystein-rich, disintegrin and a zinc metalloprotease domain. Via their metalloprotease domain, ADAMs are often implicated in ectodomain shedding, either to release e.g. growth factors or to initiate further intracellular signalling via regulated intramembrane proteolysis. Mainly based upon overexpression studies in vehicle cells, three of them, ADAMs 9, 10 and 17, have been proposed to act as alpha-secretases for amyloid precursor protein (APP). It is striking thereby that this role has since then remained somewhat ill-defined, as APP processing in ADAM9 deficient neurons is ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482580 Tue, 01 Apr 2008 04:00:00 +0100 1482580 http://www.medworm.com/index.php?rid=1482579&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%3D18393805%26dopt%3DAbstract Authors: Vincent B, Cisse MA, Sunyach C, Guillot-Sestier MV, Checler F Alzheimer's disease (AD) is by far the most common form of dementia in the elderly and concerns one out of three individuals over 85. Like other neurodegenerative disorders such as Parkinson, Hungtington or prion diseases, AD is characterized by the formation of amyloid plaques in the central nervous system. In the brain of AD patients, the main component of these abnormal deposits is an aggregated form of the so-called amyloid beta-peptide (Abeta), which is produced from a large trans-membrane type-1 protein, the beta-amyloid precursor protein (betaAPP), by the sequential action of the beta- and gamma-secretases. Beside these two amyloidogenic proteolytic attacks, betaAPP is targeted by a third enzyme termed alpha-... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482579 Tue, 01 Apr 2008 04:00:00 +0100 1482579 http://www.medworm.com/index.php?rid=1482578&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%3D18393806%26dopt%3DAbstract Authors: Nalivaeva NN, Fisk LR, Belyaev ND, Turner AJ The steady state concentration of the Alzheimer's amyloid-beta peptide in the brain represents a balance between its biosynthesis from the transmembrane amyloid precursor protein (APP), its oligomerisation into neurotoxic and stable species and its degradation by a variety of amyloid-degrading enzymes, principally metallopeptidases. These include, among others, neprilysin (NEP) and its homologue endothelin-converting enzyme (ECE), insulysin (IDE), angiotensin-converting enzyme (ACE) and matrix metalloproteinase-9 (MMP-9). In addition, the serine proteinase, plasmin, may participate in extracellular metabolism of the amyloid peptide under regulation of the plasminogen-activator inhibitor. These various amyloid-degrading enzymes have ... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482578 Tue, 01 Apr 2008 04:00:00 +0100 1482578 http://www.medworm.com/index.php?rid=1482577&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%3D18393807%26dopt%3DAbstract Authors: Hersh LB, Rodgers DW Neprilysin is a zinc metalloendopeptidase with relatively broad substrate specificity. The enzyme is localized to the plasma membrane of cells where it can function to degrade extracellular peptides. Structural studies show that neprilysin preferentially cleaves peptides on the amino side of hydrophobic amino acids. Neprilysin has been implicated in the catabolism of amyloid beta peptides in the brain and as such has received considerable attention, particularly as a therapeutic target for Alzheimer's disease. An inverse relationship between neprilysin levels and amyloid beta peptide levels and between neprilysin levels and amyloid plaque formation has been observed in human brain. Neprilysin levels decline with aging in the temporal and frontal cortex pos... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482577 Tue, 01 Apr 2008 04:00:00 +0100 1482577 http://www.medworm.com/index.php?rid=1482602&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%3D18288925%26dopt%3DAbstract Authors: Lahiri DK PMID: 18288925 [PubMed - indexed for MEDLINE] (Source: Current Alzheimer Research) Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482602 Fri, 01 Feb 2008 05:00:00 +0100 1482602 http://www.medworm.com/index.php?rid=1482601&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%3D18288926%26dopt%3DAbstract Authors: Sagin FG, Sozmen EY Advances in Alzheimer Disease (AD) research suggest that central nervous system (CNS) lipids play a key role in the pathogenesis. This role is attributed to the rich lipid content of CNS structures and the presence of blood brain barrier which disables the exchange of lipids between CNS and plasma. Among these lipids, cholesterol is a unique molecule provided mainly by its de novo synthesis in the CNS. Special apolipoproteins used for its efficient recycling within the CNS and special oxysterols formed that are specific to brain all contribute to the unique properties of the molecule. Above all, the presence of cholesterol in the membrane enables it to function as a regulator of a number of protein related processes such as the beta-amyloid precursor protei... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482601 Fri, 01 Feb 2008 05:00:00 +0100 1482601 http://www.medworm.com/index.php?rid=1482600&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%3D18288927%26dopt%3DAbstract Authors: Jaeger S, Pietrzik CU The LDL receptor gene family constitutes a class of structurally closely related cell surface receptors fulfilling diverse functions in different organs, tissues, and cell types. The LDL receptor is the prototype of this family, which also includes the VLDLR, ApoER2/LRP8, LRP1 and LRP1B, as well as Megalin/GP330, SorLA/LR11, LRP5, LRP6 and MEGF7. Recently several lines of evidence have positioned the LDL receptor gene family as one of the key players in Alzheimer's disease (AD) research. Initially this receptor family was of high interest due to its key function in cholesterol/apolipoprotein E (ApoE) uptake, with the epsilon4 allele of ApoE as the strongest genetic risk factor for late-onset AD. It has been established that the cholesterol metabolism of t... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482600 Fri, 01 Feb 2008 05:00:00 +0100 1482600 http://www.medworm.com/index.php?rid=1482599&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%3D18288928%26dopt%3DAbstract Authors: Sundaram RK, Kasinathan C, Stein S, Sundaram P Alzheimer's Disease (AD) is caused by the deposition of insoluble and toxic amyloid peptides (Abeta) in the brain leading to memory loss and other associated neurodegenerative symptoms. To date there is limited treatment options and strategies for treating AD. Studies have shown that clearance of the amyloid plaques from the brain and thus from the blood could be effective in stopping and or delaying the progression of the disease. Small peptides derived from the Abeta-42 sequence, in particular KLVFF, have shown to be effective binders of Abeta peptides and thus could be useful in delaying progression of the disease. We have taken advantage of this property by generating the retro-inverso (RI) version of this peptide, ffvlk, in d... Current Alzheimer Research journals http://www.medworm.com/rss/comments.php?id=1482599 Fri, 01 Feb 2008 05:00:00 +0100 1482599