Apolipoprotein E in Alzheimer's Disease: An Update

被引:310
作者
Yu, Jin-Tai [1 ,2 ]
Tan, Lan [1 ,2 ]
Hardy, John [3 ,4 ]
机构
[1] Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao 266071, Peoples R China
[2] Ocean Univ China, Coll Med & Pharmaceut, Qingdao 266003, Peoples R China
[3] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England
[4] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
来源
ANNUAL REVIEW OF NEUROSCIENCE, VOL 37 | 2014年 / 37卷
基金
中国国家自然科学基金;
关键词
Alzheimer's disease; apolipoprotein E; polymorphism; amyloid-beta; tau; pathogenesis; therapy; TRANSGENIC MOUSE MODEL; BETA A-BETA; REDUCES AMYLOID DEPOSITION; APOE GENOTYPE; GENETIC RISK; DEPENDENT IMPAIRMENT; BEHAVIORAL DEFICITS; GLUCOSE-METABOLISM; EPSILON-4; ALLELE; IN-VITRO;
D O I
10.1146/annurev-neuro-071013-014300
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 (APOE) 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-beta (A beta)-dependent and A beta-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/A beta interaction, modulating APOE lipidation state, and gene therapy. Accumulating evidence also suggests the utility of APOE genotyping in AD diagnosis, risk assessment, prevention, and treatment response.
引用
收藏
页码:79 / 100
页数:22
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