Bu Guojun
Hope Center for Neurological Disorders, Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
Nat Rev Neurosci. 2009 May;10(5):333-44. doi: 10.1038/nrn2620. Epub 2009 Apr 2.
The vast majority of Alzheimer's disease (AD) cases are late-onset and their development is probably influenced by both genetic and environmental risk factors. A strong genetic risk factor for late-onset AD is the presence of the epsilon4 allele of the apolipoprotein E (APOE) gene, which encodes a protein with crucial roles in cholesterol metabolism. There is mounting evidence that APOE4 contributes to AD pathogenesis by modulating the metabolism and aggregation of amyloid-beta peptide and by directly regulating brain lipid metabolism and synaptic functions through APOE receptors. Emerging knowledge of the contribution of APOE to the pathophysiology of AD presents new opportunities for AD therapy.
绝大多数阿尔茨海默病（AD）病例为晚发型，其发病可能受遗传和环境风险因素的双重影响。晚发型AD的一个强大遗传风险因素是载脂蛋白E（APOE）基因的ε4等位基因的存在，该基因编码一种在胆固醇代谢中起关键作用的蛋白质。越来越多的证据表明，APOE4通过调节淀粉样β肽的代谢和聚集，以及通过APOE受体直接调节脑脂质代谢和突触功能，从而促进AD的发病机制。APOE对AD病理生理学贡献的新认识为AD治疗带来了新机遇。
