Institute of Neurology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, China.
Neurosci Bull. 2022 Jul;38(7):809-819. doi: 10.1007/s12264-021-00814-5. Epub 2022 Feb 11.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease featuring progressive cognitive impairment. Although the etiology of late-onset AD remains unclear, the close association of AD with apolipoprotein E (APOE), a gene that mainly regulates lipid metabolism, has been firmly established and may shed light on the exploration of AD pathogenesis and therapy. However, various confounding factors interfere with the APOE-related AD risk, raising questions about our comprehension of the clinical findings concerning APOE. In this review, we summarize the most debated factors interacting with the APOE genotype and AD pathogenesis, depict the extent to which these factors relate to APOE-dependent AD risk, and discuss the possible underlying mechanisms.
阿尔茨海默病（AD）是最常见的神经退行性疾病，其特征是进行性认知障碍。虽然迟发性 AD 的病因仍不清楚，但 AD 与载脂蛋白 E（APOE）密切相关，APOE 主要调节脂质代谢，这一点已得到充分证实，可能为 AD 发病机制和治疗的探索提供线索。然而，各种混杂因素干扰了与 APOE 相关的 AD 风险，这使得我们对 APOE 相关的临床发现的理解产生了疑问。在这篇综述中，我们总结了与 APOE 基因型和 AD 发病机制相互作用的最具争议的因素，描述了这些因素与 APOE 依赖性 AD 风险的关系程度，并讨论了可能的潜在机制。
