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Abstract

The vast majority of Alzheimer's disease (AD) cases are late onset (LOAD), which is genetically complex with heritability estimates up to 80%. Apolipoprotein E () has been irrefutably recognized as the major genetic risk factor, with semidominant inheritance, for LOAD. Although the mechanisms that underlie the pathogenic nature of APOE in AD are still not completely understood, emerging data suggest that APOE contributes to AD pathogenesis through both amyloid-β (Aβ)-dependent and Aβ-independent pathways. Given the central role for APOE in the modulation of AD pathogenesis, many therapeutic strategies have emerged, including converting APOE conformation, regulating APOE expression, mimicking APOE peptides, blocking the APOE/Aβ interaction, modulating APOE lipidation state, and gene therapy. Accumulating evidence also suggests the utility of genotyping in AD diagnosis, risk assessment, prevention, and treatment response.

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2014-07-08
2024-03-29
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