Gatz M, Pedersen N L, Berg S, Johansson B, Johansson K, Mortimer J A, Posner S F, Viitanen M, Winblad B, Ahlbom A
Department of Psychology, University of Southern California, Los Angeles, USA.
J Gerontol A Biol Sci Med Sci. 1997 Mar;52(2):M117-25. doi: 10.1093/gerona/52a.2.m117.
Alzheimer's disease has been thought to have familial and sporadic forms, and several genetic defects have been identified that chiefly explain early-onset familial cases. In this study, our purpose was to detect all cases of dementia in an established twin registry and to estimate total extent of genetic contribution to liability to Alzheimer's disease.
At the first stage, members of the registry were screened for dementia, using in-person or telephone mental status testing. At the second stage, those who screened positively and their partners were referred for clinical work-ups, including neuropsychological assessment, physician examination, laboratory tests, and neuroimaging. Clinical diagnoses were assigned at a multidisciplinary consensus conference. Probandwise concordance rates were examined by zygosity, and structural modeling was applied to the data to estimate genetic and environmental influences, using both single- and multiple-threshold models.
Sixty-five pairs were identified in which one or both was demented. The probandwise concordance rate for Alzheimer's disease among monozygotic pairs was 67%; the corresponding figure for dizygotic pairs was 22%. Heritability of liability to Alzheimer's disease was estimated to be .74; to any dementia, .43. The other variance is attributable to environmental influences.
Findings indicate a substantial genetic effect for these predominantly late-onset Alzheimer's disease cases. At the same time, structural modeling results and large intra-pair differences in age of onset suggest that environmental factors are also important in determining whether and when an individual may develop dementia.
阿尔茨海默病被认为有家族性和散发性两种形式，并且已经确定了几种主要解释早发性家族性病例的基因缺陷。在本研究中，我们的目的是在一个既定的双胞胎登记处中检测所有痴呆病例，并估计基因对患阿尔茨海默病易感性的总体贡献程度。
在第一阶段，通过面对面或电话进行精神状态测试，对登记处成员进行痴呆筛查。在第二阶段，对筛查呈阳性的人员及其配偶进行临床检查，包括神经心理学评估、医生检查、实验室检测和神经影像学检查。临床诊断在多学科共识会议上确定。按先证者计算同病率，并根据合子性进行检查，同时使用单阈值模型和多阈值模型对数据进行结构建模，以估计基因和环境的影响。
共识别出65对双胞胎，其中一方或双方患有痴呆。单卵双胞胎中阿尔茨海默病的先证者同病率为67%；双卵双胞胎的相应数字为22%。患阿尔茨海默病易感性的遗传度估计为0.74；患任何痴呆的遗传度为0.43。其他变异归因于环境影响。
研究结果表明，对于这些主要为晚发性阿尔茨海默病病例，基因有显著影响。同时，结构建模结果以及发病年龄的较大双胞胎内差异表明，环境因素在决定个体是否以及何时可能患痴呆方面也很重要。
