老年痴呆的遗传机制研究进展

The genetics of Alzheimer's disease:a review of recent progress

老年痴呆症,又称阿尔茨海默病(Alzheimer’s disease,AD),是威胁老年人健康的主要疾病之一。根据发病年龄,AD可分为早发性(early-onset Alzheimer’s disease,EOAD)和迟发性(late-onset Alzheimer’s disease,LOAD)两种,两者均受到遗传因素的影响。目前已知3个致病基因导致家族性EOAD的发病:淀粉样前体蛋白基因(β-amyloid precursor protein,APP)、早老素1基因(presenilin 1,PSEN1)和早老素2基因(presenilin 2,PSEN2)。而近年来在全基因组关联分析(genome-wide association study,GWAS)等新技术的支持下,研究者相继发现并报道了一系列影响LOAD易感性的风险基因多态性位点。试对上述AD相关致病基因和主要风险基因加以简要介绍,深入探索这些基因的功能有助于对AD病理生理机制的认知。

Alzheimer＇s disease （AD） is one of the major threats to the health of aged people. The disease could be divided into two categories according to onset age. One is early-onset Alzheimer＇s disease （EOAD）, and the other is late-onset Alzheimer＇s disease （LOAD）, both influenced by genetic factors. For EOAD, three disease-causing genes have been found： the amyloid precursor protein （APP）, presenilin 1 （PSEN1）, and presenilin 2 （PSEN2）. And as to LOAD, supported by the development of new genetic analysis technologies such as genome-wide association study （GWAS） in the past few years, researchers also reported a series of risk genes altering people＇s susceptibility to the disease. In this review we give a brief introduction of the AD-related disease-causing gene mutations and the top risk gene variants showing the strongest associations with AD. Further exploring of gene functions may contribute to a better understanding of the physiopathologic mechanism of Alzheimer＇s disease.