The Gladstone Institute of Neurological Disease, University of California, San Francisco, CA 94158, USA.
Trends Mol Med. 2010 Jun;16(6):287-94. doi: 10.1016/j.molmed.2010.04.004. Epub 2010 May 27.
Human apolipoprotein (APO) E has three common isoforms that differentially affect lipid and neuronal homeostasis. APOE4, the major known genetic risk factor for Alzheimer's disease (AD), increases the occurrence and lowers the age of onset of AD. APOE4 carriers account for 65-80% of all AD cases, highlighting the importance of APOE4 in AD pathogenesis. Emerging data suggest that APOE4 contributes to AD through various pathways, some of which are dependent on amyloid-beta (Abeta). Although these Abeta-dependent roles of APOE4 have been widely studied, APOE4 has detrimental effects on neurons independent of Abeta: aberrant proteolysis of APOE4 generates neurotoxic fragments, stimulates Tau phosphorylation, which disrupts the cytoskeleton, and impairs mitochondrial function.
人类载脂蛋白（APO）E 有三种常见的亚型，它们对脂质和神经元的稳态有不同的影响。APOE4 是阿尔茨海默病（AD）的主要已知遗传风险因素，增加了 AD 的发生并降低了发病年龄。APOE4 携带者占所有 AD 病例的 65-80%，突出了 APOE4 在 AD 发病机制中的重要性。新出现的数据表明，APOE4 通过多种途径导致 AD，其中一些途径依赖于淀粉样蛋白-β（Abeta）。尽管这些 APOE4 的 Abeta 依赖性作用已被广泛研究，但 APOE4 对神经元的有害影响独立于 Abeta：APOE4 的异常蛋白水解产生神经毒性片段，刺激 Tau 磷酸化，破坏细胞骨架，并损害线粒体功能。
