神经元中ApoE与阿尔茨海默病  

An emerging role of neuronal Apolipoprotein E in the pathogenesis of Alzheimer's disease

作　　者：侯祥龙 陈椰林 Xianglong HOU;Yelin CHEN(Interdisciplinary Research Center on Biology and Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 201210,China)

机构地区：[1]中国科学院上海有机化学研究所生物与化学交叉研究中心,上海201210

出　　处：《阿尔茨海默病及相关病杂志》2025年第1期54-60,共7页Chinese Journal of Alzheimer's Disease and Related Disorders

摘　　要：不同亚型的载脂蛋白E(Apolipoprotein E,ApoE)导致阿尔茨海默病(Alzheimer's disease,AD)的发病风险不同,ApoE2降低AD风险,ApoE4增加AD风险,是AD最大的风险基因,以往的研究主要聚焦于胶质细胞分泌的ApoE对AD的影响。近年的研究发现神经元中表达的ApoE在AD进程中也发挥重要的作用,不仅影响淀粉样斑块的产生和聚集,也影响Tau蛋白的磷酸化和神经变性等病理过程。这些神经元中ApoE的功能研究为AD的治疗提供了新的思路。目前,主要在神经元中补偿表达ApoE2的AD基因治疗已经进行到二期临床试验阶段。本文对神经元中表达的ApoE对AD的影响进行了整理和归纳,为进一步理解AD的致病机理、预防和治疗提供理论参考依据。Different isoforms of Apolipoprotein E(ApoE)lead to different risks of Alzheimer's disease(AD).ApoE2 reduces the risk of AD,whereas ApoE4 is the main genetic risk factor for AD.The role of glia-secreted ApoE in the pathogenesis of AD has been extensively studied,whereas the contribution of neuronal ApoE remains largely unexplored.Recent studies have found that ApoE is also expressed in neurons,where it plays important roles in the pathogenesis of AD,including regulation of amyloid plaque seeding and growth,phosphorylation of Tau,and neurodegeneration,etc.Based on these studies,a gene therapeutic strategy using adeno-associated virus(AAV)to express ApoE2 in neurons is now in that phase II clinical trials for AD treatment.This article summarizes the knowledge about the emerging role of neuronal ApoE in AD pathogenesis.

关 键 词：载脂蛋白E 阿尔茨海默病 神经元 

分 类 号：R74[医药卫生—神经病学与精神病学]