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Optimized Turmeric Extracts Have Potent Anti-amyloidogenic Effects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 c...
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Shytle RD, Bickford PC, Rezai-Zadeh K, Houb L, Zeng J, Tana J, Sanberg PR, Sanberg CD, Roschek B, Fink RC, Alberte RS Tags: Curr Alzheimer Res Source Type: journals

Alzheimer's Disease and Retinal Neurodegeneration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 shielde...
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Guo L, Duggan J, Cordeiro MF Tags: Curr Alzheimer Res Source Type: journals

Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) Patients are Characterized by Increased BDNF Serum Levels.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 po...
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Angelucci F, Spalletta G, di Iulio F, Ciaramella A, Salani F, Colantoni L, Varsi AE, Gianni W, Sancesario G, Caltagirone C, Bossù P Tags: Curr Alzheimer Res Source Type: journals

Association Constants of Pyridine and Piperidine Alkaloids to Amyloid ss Peptide Determined by Electrochemical Impedance Spectroscopy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ap...
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Grabowska I, Radecka H, Burza A, Radecki J, Kaliszan M, Kaliszan R Tags: Curr Alzheimer Res Source Type: journals

Functional, Global and Cognitive Decline Correlates to Accumulation of Alzheimer's Pathology in MCI and AD.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Sabbagh MN, Cooper K, Justin Delange D, Stoehr JD, Thind K, Tyson Lahti R, Reisberg B, Sue L, Vedders L, Fleming SR, Thomas P, Beach G Tags: Curr Alzheimer Res Source Type: journals

Familial Alzheimer's Disease Mutations in Presenilin 1 Do Not Alter Levels of the Secreted Amyloid-beta Protein Precursor Generated by beta-Secretase Cleavage.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Zhang C, Browne A, Kim DY, Tanzi RE Tags: Curr Alzheimer Res Source Type: journals

Cholesterol, Lipids, Amyloid Beta, and Alzheimer's.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 int...
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Vestergaard M, Hamada T, Morita M, Takagi M Tags: Curr Alzheimer Res Source Type: journals

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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 ne...
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Gorham P, Bark N, Björkhem , Meaney S, Crisby M Tags: Curr Alzheimer Res Source Type: journals

Assessing the Relationship between Health Utilities, Quality of Life, and Health Care Costs in Alzheimer's Disease: The CATIE-AD Study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Miller EA, Rosenheck RA, Schneider LS Tags: Curr Alzheimer Res Source Type: journals

Genetic Susceptibility to Behavioural and Psychological Symptoms in Alzheimer Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Current Alzheimer Research - September 2, 2009 Category: Neurology Authors: Borroni B, Costanzi C, Padovani A Tags: Curr Alzheimer Res Source Type: journals

Addressing Alzheimer's Disease Tangles: From NAP to AL-108.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 s...
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Gozes I, Stewart A, Morimoto B, Fox A, Sutherland K, Schmeche D Tags: Curr Alzheimer Res Source Type: journals

O-Glcnac Modification and the Tauopathies: Insights from Chemical Biology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 phosphor...
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Yuzwa SA, Vocadlo DJ Tags: Curr Alzheimer Res Source Type: journals

Tau-Focused Immunotherapy for Alzheimer's Disease and Related Tauopathies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 hyper...
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Sigurdsson EM Tags: Curr Alzheimer Res Source Type: journals

Lysosomal Modulatory Drugs for a Broad Strategy Against Protein Accumulation Disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Bahr BA Tags: Curr Alzheimer Res Source Type: journals

A PPardelta Agonist Reduces Amyloid Burden and Brain Inflammation in a Transgenic Mouse Model of Alzheimer's Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 insuli...
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Kalinin S, Richardson JC, Feinstein DL Tags: Curr Alzheimer Res Source Type: journals

Suppression of Glial HO-1 Activitiy as a Potential Neurotherapeutic Intervention in AD.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 as...
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Schipper HM, Gupta A, Szarek WA Tags: Curr Alzheimer Res Source Type: journals

A Neurotrophic Rationale for the Therapy of Neurodegenerative Disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Saragovi HU, Hamel E, Di Polo A Tags: Curr Alzheimer Res Source Type: journals

Understanding the Basis for the Association of Apoe4 with Alzheimer's Disease: Opening the Door for Therapeutic Approaches.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Zhong N, Weisgraber KH Tags: Curr Alzheimer Res Source Type: journals

Modulation and Detection of Tau Aggregation with Small-Molecule Ligands.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ligan...
Source: Current Alzheimer Research - August 13, 2009 Category: Neurology Authors: Chang E, Honson NS, Bandyopadhyay B, Funk KE, Jensen JR, Kim S, Naphade S, Kuret J Tags: Curr Alzheimer Res Source Type: journals

Memory and consciousness in Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Souchay C, Moulin CJ Tags: Curr Alzheimer Res Source Type: journals

A common biological mechanism in cancer and Alzheimer's disease?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Behrens MI, Lendon C, Roe CM Tags: Curr Alzheimer Res Source Type: journals

Cell cycle re-entry in Alzheimer's disease: a major neuropathological characteristic?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 b...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Lopes JP, Oliveira CR, Agostinho P Tags: Curr Alzheimer Res Source Type: journals

The role of IGF-1 receptor and insulin receptor signaling for the pathogenesis of Alzheimer's disease: from model organisms to human disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 (...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Freude S, Schilbach K, Schubert M Tags: Curr Alzheimer Res Source Type: journals

The role of vascular factors in late-onset sporadic Alzheimer's disease. Genetic and molecular aspects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 patient...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Rocchi A, Orsucci D, Tognoni G, Ceravolo R, Siciliano G Tags: Curr Alzheimer Res Source Type: journals

Neuronal response of peroxisomal and peroxisome-related proteins to chronic and acute Abeta injury.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, dem...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Cimini A, Benedetti E, D'Angelo B, Cristiano L, Falone S, Di Loreto S, Amicarelli F, Cerù MP Tags: Curr Alzheimer Res Source Type: journals

Accelerated fibrillation of alpha-synuclein induced by the combined action of macromolecular crowding and factors inducing partial folding.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Munishkina LA, Fink AL, Uversky VN Tags: Curr Alzheimer Res Source Type: journals

Thin, stubby or mushroom: spine pathology in Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 alteration...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Tackenberg C, Ghori A, Brandt R Tags: Curr Alzheimer Res Source Type: journals

Increased CRMP2 phosphorylation is observed in Alzheimer's disease; does this tell us anything about disease development?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 importa...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Soutar MP, Thornhill P, Cole AR, Sutherland C Tags: Curr Alzheimer Res Source Type: journals

Prediction of conversion from mild cognitive impairment to Alzheimer's disease by CSF cytochrome c levels and N200 latency.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 signifi...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Papaliagkas VT, Anogianakis G, Tsolaki MN, Koliakos G, Kimiskidis VK Tags: Curr Alzheimer Res Source Type: journals

Detection of Amyloid-beta aggregates in body fluids: a suitable method for early diagnosis of Alzheimer's disease?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Funke SA, Birkmann E, Willbold D Tags: Curr Alzheimer Res Source Type: journals

Safety of lumbar puncture procedures in patients with Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Peskind E, Nordberg A, Darreh-Shori T, Soininen H Tags: Curr Alzheimer Res Source Type: journals

Music therapy for individuals with dementia: areas of interventions and research perspectives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Raglio A, Gianelli MV Tags: Curr Alzheimer Res Source Type: journals

Towards retinoid therapy for Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology Authors: Shudo K, Fukasawa H, Nakagomi M, Yamagata N Tags: Curr Alzheimer Res Source Type: journals

Amyloid PET and MRI in Alzheimer's disease and mild cognitive impairment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Current Alzheimer Research - May 31, 2009 Category: Neurology 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 Tags: Curr Alzheimer Res Source Type: journals

Advances in Alzheimer therapy: understanding pharmacological approaches to the disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 discipline...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Martínez A, Lahiri DK, Giacobini E, Greig NH Tags: Curr Alzheimer Res Source Type: journals

Cholinesterase inhibitors and beyond.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Ch...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Pepeu G, Giovannini MG Tags: Curr Alzheimer Res Source Type: journals

Responders to ChEI treatment of Alzheimer's disease show restitution of normal regional cortical activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Venneri A, McGeown WJ, Shanks MF Tags: Curr Alzheimer Res Source Type: journals

M1 agonists as a potential disease-modifying therapy for Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 restor...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Caccamo A, Fisher A, LaFerla FM Tags: Curr Alzheimer Res Source Type: journals

GEPT extract reduces Abeta deposition by regulating the balance between production and degradation of Abeta in APPV717I transgenic mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Tian J, Shi J, Zhang L, Yin J, Hu Q, Xu Y, Sheng S, Wang P, Ren Y, Wang R, Wang Y Tags: Curr Alzheimer Res Source Type: journals

Oligomeric amyloid beta-protein as a therapeutic target in Alzheimer's disease: its significance based on its distinct localization and the occurrence of a familial variant form.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Ito K, Ishibashi K, Tomiyama T, Umeda T, Yamamoto K, Kitajima E, Idomoto T, Nagatomo T, Mori H Tags: Curr Alzheimer Res Source Type: journals

Visualization of brain amyloid and microglial activation in mouse models of Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Higuchi M Tags: Curr Alzheimer Res Source Type: journals

Long-term follow-up of patients immunized with AN1792: reduced functional decline in antibody responders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - index...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Vellas B, Black R, Thal LJ, Fox NC, Daniels M, McLennan G, Tompkins C, Leibman C, Pomfret M, Grundman M, Tags: Curr Alzheimer Res Source Type: journals

Early Tau pathology involving the septo-hippocampal pathway in a Tau transgenic model: relevance to Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 le...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Belarbi K, Schindowski K, Burnouf S, Caillierez R, Grosjean ME, Demeyer D, Hamdane M, Sergeant N, Blum D, Buée L Tags: Curr Alzheimer Res Source Type: journals

Development of a non invasive NGF-based therapy for Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. ...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Covaceuszach S, Capsoni S, Ugolini G, Spirito F, Vignone D, Cattaneo A Tags: Curr Alzheimer Res Source Type: journals

Natural non-trasgenic animal models for research in Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 th...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Sarasa M, Pesini P Tags: Curr Alzheimer Res Source Type: journals

Structural and functional MRI in mild cognitive impairment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Alzheimer Research - March 31, 2009 Category: Neurology Authors: Pihlajamäki M, Jauhiainen AM, Soininen H Tags: Curr Alzheimer Res Source Type: journals

Celebrating the fifth year anniversary of current Alzheimer research.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19199869 [PubMed - in process] (Source: Current Alzheimer Research)
Source: Current Alzheimer Research - February 1, 2009 Category: Neurology Authors: Lahiri DK Tags: Curr Alzheimer Res Source Type: journals

Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Alzheimer Research - February 1, 2009 Category: Neurology Authors: Nordberg A, Darreh-Shori T, Peskind E, Soininen H, Mousavi M, Eagle G, Lane R Tags: Curr Alzheimer Res Source Type: journals

Cholesterol in Alzheimer's disease: unresolved questions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 chole...
Source: Current Alzheimer Research - February 1, 2009 Category: Neurology Authors: Stefani M, Liguri G Tags: Curr Alzheimer Res Source Type: journals

Anesthesia, calcium homeostasis and Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 iso...
Source: Current Alzheimer Research - February 1, 2009 Category: Neurology Authors: Wei H, Xie Z Tags: Curr Alzheimer Res Source Type: journals