Departments of Neurology, Pathology and Psychiatry, Center for Cognitive Neurology, NYU School of Medicine, Science Building, Rm 1017, 435 East 30(th) Street, New York, NY 10016, USA.
Brain & Mind Centre and Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Neurobiol Dis. 2020 May;138:104784. doi: 10.1016/j.nbd.2020.104784. Epub 2020 Feb 4.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder that is growing in prevalence globally. It is the only major cause of death without any effective pharmacological means to treat or slow progression. Inheritance of the ε4 allele of the Apolipoprotein (APO) E gene is the strongest genetic risk factor for late-onset AD. The interaction between APOE and amyloid β (Aβ) plays a key role in AD pathogenesis. The APOE-Aβ interaction regulates Aβ aggregation and clearance and therefore directly influences the development of amyloid plaques, congophilic amyloid angiopathy and subsequent tau related pathology. Relatively few AD therapeutic approaches have directly targeted the APOE-Aβ interaction thus far. Here we review the critical role of APOE in the pathogenesis of AD and some of the most promising therapeutic approaches that focus on the APOE-Aβ interaction.
阿尔茨海默病(AD)是一种破坏性的神经退行性疾病,在全球范围内的发病率不断上升。它是唯一一种没有任何有效药物治疗或减缓其进展的主要死因。载脂蛋白(APO)E 基因的 ε4 等位基因遗传是晚发性 AD 的最强遗传风险因素。APOE 与淀粉样蛋白-β(Aβ)之间的相互作用在 AD 发病机制中起着关键作用。APOE-Aβ 相互作用调节 Aβ 的聚集和清除,因此直接影响淀粉样斑块、亲神经淀粉样血管病和随后的 tau 相关病理学的发展。迄今为止,相对较少的 AD 治疗方法直接针对 APOE-Aβ 相互作用。本文综述了 APOE 在 AD 发病机制中的关键作用,以及一些最有前途的治疗方法,这些方法主要集中在 APOE-Aβ 相互作用上。