Breitner J C, Folstein M F, Murphy E A
J Psychiatr Res. 1986;20(1):31-43. doi: 10.1016/0022-3956(86)90021-x.
An autosomal dominant genetic etiology has been proposed for Alzheimer Dementia (AD), but many cases appear to be sporadic. Evaluation of the possible genetic transmission of AD from its familial aggregation requires consideration of (1) the proportion of index cases with genetic disease, and (2) the consequences of typically very late onset. To investigate these factors, a provisional biomathematical genetic model was developed from the empirical age-specific incidence of AD in relatives. Based upon the premise of an autosomal dominant AD gene in proband families, the modeling technique provides estimates of the proportion of genetic index cases (as opposed to phenocopies) and the parameters of age-dependent gene expression. With appropriate parameters the model accurately reflects the age-specific familial risk of AD, suggesting the appropriateness of its underlying assumptions. The estimated proportions of genetic index cases suggest that heritable disease constitutes a majority of AD. In cases ascertained by the presence of aphasia or apraxia the estimated proportion of genetic cases is 100%. The greatest likelihood of gene expression is in the ninth decade, however, suggesting that most genetically predisposed relatives will die from other causes before developing AD.
阿尔茨海默病性痴呆（AD）被认为有常染色体显性遗传病因，但许多病例似乎是散发性的。从家族聚集性评估AD可能的遗传传递需要考虑：（1）患有遗传性疾病的索引病例比例；（2）通常发病很晚的后果。为了研究这些因素，根据亲属中AD的年龄特异性发病率建立了一个临时生物数学遗传模型。基于先证者家族中常染色体显性AD基因的前提，该建模技术可估计遗传索引病例（与表型相似病例相对）的比例以及年龄依赖性基因表达的参数。通过适当的参数，该模型能准确反映AD的年龄特异性家族风险，表明其基本假设的合理性。遗传索引病例的估计比例表明，遗传性疾病构成了AD的大多数。在因失语或失用症确诊的病例中，遗传病例的估计比例为100%。然而，基因表达的最大可能性出现在九十岁，这表明大多数具有遗传易感性的亲属在患AD之前会死于其他原因。
