ABCA7与阿尔茨海默病的研究进展

ABCA7 and Alzheimer’s Disease Pathogenesis

阿尔茨海默病(Alzheimer’s disease,AD)是一种严重的中枢神经系统退行性疾病,也是老年人痴呆最常见的原因,其病因目前尚未阐明。三磷酸腺苷结合盒转运体A7(ATP-binding cassette transporter A7,ABCA7)在脑中有较高的表达水平,参与脑内脂质代谢、吞噬作用以及免疫反应等过程。自从全基因组关联研究将ABCA7确定为AD的风险基因以后,越来越多的来自体内外和基于人的研究证实,ABCA7是早发和迟发型AD最重要的风险基因之一。本文对ABCA7在AD发生发展中的作用进行综述,以期为AD的防治提供新的治疗靶点和途径。

Alzheimer’s disease(AD),a serious degenerative disease of the central nervous system,is the most common cause of dementia in the elderly.Its etiology has not yet been elucidated.ATP-binding cassette transporter A7(ABCA7)has a high level expression in the brain.Since the genome-wide association studies identified ABCA7 as a risk gene for AD,more and more evidence from in vitro,in vivo,and human-based studies has confirmed that ABCA7 is one of the most important risk genes for early-onset and late-onset AD.ABCA7mediates phospholipid efflux and its distribution in neurons,and plays a weak but significant role in cholesterol regulation,so as to maintain the lipid homeostasis in the brain.ABCA7 is also closely related to microglia phagocytosis and immune function.When lipid homeostasis in the brain is unbalanced or ABCA7 is defective,it will reduce the ability of microglia to process Aβ,causing abnormal accumulation of Aβand triggering the inflammatory response in the brain.ABCA7 single nucleotide polymorphism(SNP)variants or loss-of-function(LOF)mutations are also significantly associated to the risk of AD.We suggest that ABCA7 may be a potential biomarker or therapeutic target for early detection and diagnosis of AD.In this paper,the role of ABCA7 in the occurrence and development of AD is reviewed,in order to provide therapeutic ideas for the clinical prevention and treatment of AD.