Ashford J Wesson, Mortimer James A
Department of Psychiatry, Sanders-Brown Center on Aging, University of Kentucky, Veterans Affairs Medical Center, Lexington, KY 40536-0230, USA.
J Alzheimers Dis. 2002 Jun;4(3):169-77. doi: 10.3233/jad-2002-4307.
This team takes the position that what is commonly referred to as non-familial Alzheimer's disease (AD) is predominantly due to genetic factors. Population-based studies suggest that genetic factors cause the majority of cases that begin after age 60. There are several lines of evidence supporting this position: Data from the Nun Study suggest that the risk for AD is largely established by early adulthood, implying that later adult exposures likely play only a small role in causation. Family studies show that first-degree blood relatives of persons with non-familial AD have a substantially increased risk of AD relative to controls. Twin studies suggest that the heritability of AD exceeds 60%. Environmental factors, such as socioeconomic status, education, and head injury, are strong risk factors for AD only in individuals with a genetic predisposition. The APOE genotype is a powerful risk factor for AD and accounts for as much as 50%. There are numerous other candidate genes with strong associations with AD that presumably explain the remaining population risk. This paper further reviews the mechanisms associated with AD causation for APOE and other candidate genes and implications for the development of prevention strategies.
该团队认为，通常所说的非家族性阿尔茨海默病（AD）主要是由遗传因素导致的。基于人群的研究表明，遗传因素导致了大多数60岁以后发病的病例。有几条证据支持这一观点：修女研究的数据表明，AD的风险在成年早期基本就已确定，这意味着成年后期的接触因素在病因中可能只起很小的作用。家族研究表明，非家族性AD患者的一级血亲患AD的风险相对于对照组大幅增加。双胞胎研究表明，AD的遗传度超过60%。环境因素，如社会经济地位、教育程度和头部受伤，仅在有遗传易感性的个体中是AD的强风险因素。APOE基因型是AD的一个强大风险因素，占比高达50%。还有许多其他与AD有强关联的候选基因，大概可以解释其余的人群风险。本文进一步综述了与APOE和其他候选基因导致AD相关的机制以及对预防策略制定的影响。
