Journal of Alzheimer's Disease - Volume 17, issue 1

Article Type: Obituary

DOI: 10.3233/JAD-2009-1039

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 1-3, 2009

Article Type: Other

DOI: 10.3233/JAD-2009-1097

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 5-5, 2009

Authors: Panza, Francesco | Capurso, Cristiano | D'Introno, Alessia | Colacicco, Anna M. | Frisardi, Vincenza | Lorusso, Maria | Santamato, Andrea | Seripa, Davide | Pilotto, Alberto | Scafato, Emanuele | Vendemiale, Gianluigi | Capurso, Antonio | Solfrizzi, Vincenzo

Article Type: Review Article

Abstract: Among lifestyle-related factors, low to moderate alcohol drinking has been proposed as a protective factor against the development of age-related changes in cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD) in several longitudinal studies, but contrasting findings also exist. Furthermore, many of these studies were limited by cross-sectional design, restriction by age or sex, or incomplete ascertainment. Different outcomes, beverages, drinking patterns, or follow-up periods, or possible interactions with other lifestyle-related (i.e., smoking) or genetic factors [i.e., apolipoprotein E (APOE) genotyping] may be sources of great variability. Light to moderate …alcohol use may be associated with a reduced risk of unspecified incident dementia and AD, while for VaD, cognitive decline, and predementia syndromes, the current evidence is only suggestive of a protective effect. In conclusion, as intervention studies are not feasible in this area, the best evidence comes from an overview of epidemiological studies, suggesting that the protective effects are more likely with wine consumption and the absence of an APOE e4 allele. At present, there is no indication that light to moderate alcohol drinking would be harmful to cognition and dementia, and it is not possible to define a specific beneficial level of alcohol intake. Show more

Keywords: Alcohol, Alzheimer's disease, dementia, mild cognitive impairment, predementia syndromes, vascular dementia, vascular risk factors

DOI: 10.3233/JAD-2009-1009

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 7-31, 2009

Authors: Amijee, Hozefa | Scopes, David I.C.

Article Type: Review Article

Abstract: Amyloid-β (Aβ) peptide is one of the most promising targets for the development of new therapies for Alzheimer's disease (AD). A growing body of evidence suggests a key pathogenic role for soluble oligomers of Aβ, and therapeutics which block the generation of toxic Aβ assemblies may provide successful new treatments for AD. This is therapeutically attractive because the aggregation process is believed to be an exclusively pathological event and therefore compounds targeting this mechanism are more likely to have an acceptable safety profile. A number of studies have shown that AD severity correlates more closely with soluble oligomeric forms of …Aβ than with fibrillar forms of the peptide. Thus, blocking the initial stages of Aβ aggregation with small molecules could hold considerable promise as an entry to new therapies for AD. The rapid development in our understanding of toxic amyloid assemblies now provides fresh impetus for this interesting approach, and this review assesses the status of drug development in this area. Recent progress with clinical studies and highlights of new structural series that are showing promise in the discovery/pre-clinical phase are discussed. Show more

Keywords: Aggregation, amyloid-β, inhibitor, neurotoxicity, oligomer

DOI: 10.3233/JAD-2009-1044

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 33-47, 2009

Authors: Mao, Zixu

Article Type: Article Commentary

DOI: 10.3233/JAD-2009-1025

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 49-51, 2009

Authors: de Bot, Susanne T. | Kremer, H.P.H. | Dooijes, Dennis | Verbeek, Marcel M.

Article Type: Short Communication

Abstract: In sporadic Alzheimer's disease (AD), cerebrospinal fluid (CSF) analysis is becoming increasingly relevant to establish an early diagnosis. We present a case of familial AD due to a presenilin-1 mutation in which CSF studies suggested appropriate DNA diagnostics. A 38 year old Dutch man presented with dementia, spastic paraparesis, and frontal executive function impairments, mimicking familial Creutzfeldt Jakob disease and frontotemporal dementia. CSF studies, revealing increased total tau and phosphorylated-tau levels with decreased amyloid-β42 , distinguished familial AD from Creutzfeldt Jakob disease and frontotemporal dementia. A causative p.L424R PSEN1 mutation was subsequently identified.

Keywords: Amyloid-β42, cerebrospinal fluid biomarkers, familial Alzheimer's disease, phosphorylated-tau, p.L424R, presenilin-1 mutation, tau protein

DOI: 10.3233/JAD-2009-1038

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 53-57, 2009

Authors: Origlia, Nicola | Capsoni, Simona | Cattaneo, Antonino | Fang, Fang | Arancio, Ottavio | Yan, Shi Du | Domenici, Luciano

Article Type: Research Article

Abstract: Oligomeric amyloid-β (Aβ) interferes with long term potentiation (LTP) and cognitive processes, suggesting that Aβ peptides may play a role in the neuronal dysfunction which characterizes the early stages of Alzheimer's disease (AD). Multiple lines of evidence have highlighted RAGE (receptor for advanced glycation end-products) as a receptor involved in Aβ-induced neuronal and synaptic dysfunction. In the present study, we investigated the effect of oligomeric soluble Aβ1-42 on LTP elicited by the stimulation of different intracortical pathways in the mouse visual cortex. A variety of nanomolar concentrations (20–200 nM) of Aβ1-42 were able to inhibit LTP in cortical …layer II-III induced by either white matter (WM-Layer II/III) or the layer II/III (horizontal pathway) stimulation, whereas the inhibition of LTP was more susceptible to Aβ1-42 , which occurred at 20 nM of Aβ, when stimulating layer II-III horizontal pathway. Remarkably, cortical slices were resistant to nanomolar Aβ1-42 in the absence of RAGE (genetic deletion of RAGE) or blocking RAGE by RAGE antibody. These results indicate that nanomolar Aβ inhibits LTP expression in different neocortical circuits. Crucially, it is demonstrated that Aβ-induced reduction of LTP in different cortical pathways is mediated by RAGE. Show more

Keywords: Alzheimer's disease, amyloid-β, neocortical areas, RAGE, synaptic plasticity

DOI: 10.3233/JAD-2009-1045

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 59-68, 2009

Authors: Sohrabi, Hamid R. | Bates, Kristyn A. | Rodrigues, Mark | Taddei, Kevin | Martins, Georgia | Laws, Simon M. | Lautenschlager, Nicola T. | Dhaliwal, Satvinder S. | Foster, Jonathan K. | Martins, Ralph N.

Article Type: Research Article

Abstract: Apolipoprotein E ε4 (APOE-ε4) is a major genetic risk factor for Alzheimer's disease. In this study, we addressed the question of whether possession of the APOE-ε4 allele results in adverse effects on perceived health-related quality of life (HRQL) and on symptoms of depression and anxiety in people with subjective memory complaints (SMC). 138 healthy, community-dwelling elderly volunteers, aged 52 to 85, were assessed for HRQL, depression, and anxiety. The participants were classified as i) APOE-ε4 carriers or ii) non-carriers with a) SMC or b) without memory complaints. The possible interactions of APOE genotype, gender, and SMC on HRQL, depression, and …anxiety were investigated statistically. SMC was significantly associated with poorer outcomes on measures of depression, trait anxiety, and mental health. APOE-ε4 carriers did not significantly differ from non-carriers on HRQL, depression, and anxiety. However, significant interaction was found between APOE-ε4 genotype and SMC on depression. These findings are important from a health perspective and suggest that memory complaints are associated with markers of mental health and quality of life that are independent of possession of the APOE-ε4 allele, despite the importance of this polymorphism in the risk of AD and other health problems. Show more

Keywords: Alzheimer's disease, anxiety, APOE-ε4, depression, health-related quality of life (HRQL), subjective memory complaints

DOI: 10.3233/JAD-2009-1018

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 69-79, 2009

Authors: Suwalsky, Mario | Bolognin, Silvia | Zatta, Paolo

Article Type: Research Article

Abstract: A number of observations indicate that the primary target of amyloid-β (Aβ) peptide is the cellular membrane of neurons. In the context of these observations we investigated, using X-ray diffraction techniques, whether Aβ-metal complexes were able to affect lipid bilayers as a model of cell membranes. The binding of Al to Aβ gave particular conformational properties to the peptide that led to a marked alteration of the lipid bilayer representing phospholipids located in the outer monolayer of cell membranes. This effect was peculiar, since in our experimental conditions Aβ alone did not affect the lipid architecture, whereas the Al salt …did, but only at concentrations several orders of magnitude higher than those of the Aβ-Al complex. In accordance with the effects observed with lipid bilayers, studies with human neuroblastoma cells demonstrated an impairment of cell functioning only in the presence of Aβ-Al complex. Our findings imply that Al, compared to the other Aβ-metal complexes tested, could have a specifically relevant effect in enhancing Aβ toxicity. Show more

Keywords: Alzheimer's disease, amyloid-β, biometals, cell membrane, lipid bilayer

DOI: 10.3233/JAD-2009-1032

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 81-90, 2009

Authors: Larbi, Anis | Pawelec, Graham | Witkowski, Jacek M. | Schipper, Hyman M. | Derhovanessian, Evelyna | Goldeck, David | Fulop, Tamas

Article Type: Research Article

Abstract: The distribution of peripheral T cell subsets in young and healthy old people is markedly different, characterized by decreased numbers of naïve cells and increased numbers and clonal expansions of memory cells, predominantly in the CD8+ MHC class I-restricted subset. Here, however, we document dramatic alterations in naïve and memory subsets of CD4+ cells in patients with mild Alzheimer's disease (AD), with greatly decreased percentages of naïve cells, elevated memory cells, and increased proportions of CD4+ but not CD8+ cells lacking the important costimulatory receptor CD28. CD4+CD25high potentially T regulatory cells with a naïve phenotype are also reduced in …AD patients. Together these data provide stronger evidence than hitherto presented for more highly differentiated CD4+ as well as CD8+ T cells in AD patients, consistent with an adaptive immune system undergoing persistent antigenic challenge and possibly manifesting dysregulation as a result. Show more

Keywords: Alzheimer's disease, immunosenescence, polychromatic flow cytometry, T cell subsets

DOI: 10.3233/JAD-2009-1015

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 91-103, 2009