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      Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

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          Abstract

          Alzheimer's disease (AD)—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE), the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD.

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          Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.

          Lars Bertram, Matthew B. McQueen, Kristina Mullin … (2007)
          The past decade has witnessed hundreds of reports declaring or refuting genetic association with putative Alzheimer disease susceptibility genes. This wealth of information has become increasingly difficult to follow, much less interpret. We have created a publicly available, continuously updated database that comprehensively catalogs all genetic association studies in the field of Alzheimer disease (http://www.alzgene.org). We performed systematic meta-analyses for each polymorphism with available genotype data in at least three case-control samples. In addition to identifying the epsilon4 allele of APOE and related effects, we pinpointed over a dozen potential Alzheimer disease susceptibility genes (ACE, CHRNB2, CST3, ESR1, GAPDHS, IDE, MTHFR, NCSTN, PRNP, PSEN1, TF, TFAM and TNF) with statistically significant allelic summary odds ratios (ranging from 1.11-1.38 for risk alleles and 0.92-0.67 for protective alleles). Our database provides a powerful tool for deciphering the genetics of Alzheimer disease, and it serves as a potential model for tracking the most viable gene candidates in other genetically complex diseases.
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            The role of apolipoprotein E in Alzheimer's disease.

            Jungsu Kim, Jacob Basak, David Holtzman (2009)
            The epsilon4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Abeta aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE epsilon4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.
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              Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors.

              Raj Kalaria, Gladys Maestre, Raul Arizaga … (2008)
              Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Alzheimers Dis
                Journal ID (publisher-id): IJAD
                Title: International Journal of Alzheimer's Disease
                Publisher: SAGE-Hindawi Access to Research
                ISSN (Electronic): 2090-0252
                Publication date Collection: 2011
                Publication date (Electronic): 5 April 2011
                Volume: 2011
                Electronic Location Identifier: 974361
                Affiliations
                1Department of Psychiatry, Douglas Mental Health University Institute, Perry Pavilion, E-3207.1, 6875 Lasalle Boulevard, Verdun, QC, Canada H4H1R3
                2Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada H3A2B4
                3McGill Centre for Studies in Aging, Verdun, QC, Canada H4H1R3
                Author notes

                Academic Editor: Mikko Hiltunen

                Article
                DOI: 10.4061/2011/974361
                PMC ID: 3089878
                PubMed ID: 21559182
                SO-VID: 6fa147b3-c724-4c54-a4ff-497192972c53
                Copyright © Copyright © 2011 Valérie Leduc et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 November 2010
                Date accepted : 9 February 2011
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Neurology
                Data availability:
                ScienceOpen disciplines: Neurology

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