载脂蛋白E
痴呆
疾病
等位基因
基因亚型
阿尔茨海默病
生物
发病机制
神经科学
遗传学
基因
医学
内科学
免疫学
作者
Yuka A. Martens,Na Zhao,Chia‐Chen Liu,Takahisa Kanekiyo,Austin J. Yang,Alison Goate,David M. Holtzman,Guojun Bu
出处
期刊:Neuron
[Elsevier]
日期:2022-04-01
卷期号:110 (8): 1304-1317
被引量:129
标识
DOI:10.1016/j.neuron.2022.03.004
摘要
The ε4 allele of the apolipoprotein E gene (APOE4) is a strong genetic risk factor for Alzheimer's disease (AD) and several other neurodegenerative conditions, including Lewy body dementia (LBD). The three APOE alleles encode protein isoforms that differ from one another only at amino acid positions 112 and 158: apoE2 (C112, C158), apoE3 (C112, R158), and apoE4 (R112, R158). Despite progress, it remains unclear how these small amino acid differences in apoE sequence among the three isoforms lead to profound effects on aging and disease-related pathways. Here, we propose a novel "ApoE Cascade Hypothesis" in AD and age-related cognitive decline, which states that the biochemical and biophysical properties of apoE impact a cascade of events at the cellular and systems levels, ultimately impacting aging-related pathogenic conditions including AD. As such, apoE-targeted therapeutic interventions are predicted to be more effective by addressing the biochemical phase of the cascade.
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