基于APOEε4等位基因分型的阿尔茨海默病发病机制及诊疗研究新视角

New insights into pathogenesis,diagnosis and treatment of Alzheimer's disease based on APOEε4 allele

近年来研究发现,阿尔茨海默病(AD)复杂的病理表现无法完全用β-淀粉样蛋白(Aβ)级联反应假说解释,同时靶向Aβ药物治疗效果欠佳的现况也使得研究人员对该假说提出质疑。概率载脂蛋白E(APOE)假说在肯定Aβ致病作用的基础上,也强调了APOE基因在AD疾病进展、临床诊断及治疗选择中发挥着重要作用,并提出在进行AD诊断前应先根据受试者携带APOEε4等位基因与否进行分组,然后按Aβ沉积/tau蛋白神经原纤维缠结/神经退行性变进行分型诊断。本文现围绕3种基于APOEε4等位基因分型的AD(常染色体显性AD、APOEε4等位基因相关散发性AD和APOE?4等位基因无关散发性AD)的发病机制及诊疗研究进展进行综述,以期从新视角理解APOEε4等位基因在AD中的重要性。

In recent years,it has been found that complex pathological manifestations of Alzheimer's disease(AD)cannot be fully explained byβ-amyloid(Aβ)cascade hypothesis,and researchers question this hypothesis resulting from the poor effect of targeted Aβdrugs.Probabilistic apolipoprotein E(APOE)hypothesis affirms the Aβpathogenesis but also emphasizes the important role of APOE gene in diagnosis,treatment and progression of AD.In AD diagnosis,subjects should be firstly grouped according to presence or absence of APOEε4 allele,and then classified according to Aβdeposition/tau neurofibrillary tangles/neurodegeneration.This article reviews the recent advance in the pathogenesis,diagnosis and treatment of 3 types of AD variants(autosomal dominant AD,sporadic AD related to APOEε4,and sporadic AD unrelated to APOEε4),with a view to understand the importance of APOEε4 allele in AD from a new perspective.