Breitner J C, Murphy E A, Folstein M F
J Psychiatr Res. 1986;20(1):45-55. doi: 10.1016/0022-3956(86)90022-1.
A biomathematical genetic model for the age-specific risk of Alzheimer Dementia (AD) was applied to two problems in the clinical genetics of this disorder. In a test of the ability of a clinical marker specifically to identify genetic AD, cases grouped by the phenotype of amnesia with aphasia or apraxia (aaa) were shown to have familial risk that suggested a pure genetic illness, and differed significantly (p = 0.006) from cases without this phenotype. The model was also used in a Bayesian paradigm to assess the probability that individual cases had hereditary disease, given their family history. Here the results were surprisingly ambiguous: Even with no affected relatives, there is a substantial likelihood that many AD cases may have a genetic illness. Hence, one cannot reliably classify individual cases as "familial" or "sporadic" from family history alone. The phenotype of aaa (or other suitable marker) appears to be more reliable than the degree of manifest familial aggregation as an indicator of genetic AD.
一个针对阿尔茨海默病（AD）特定年龄风险的生物数学遗传模型被应用于该疾病临床遗传学的两个问题。在一项关于临床标志物特异性识别遗传性AD能力的测试中，按失忆伴失语或失用症（aaa）表型分组的病例显示出家族风险，提示为纯遗传性疾病，且与无该表型的病例有显著差异（p = 0.006）。该模型还被用于贝叶斯范式中，根据个体的家族史评估其患遗传性疾病的概率。在此，结果出人意料地不明确：即使没有受影响的亲属，许多AD病例仍有很大可能性患有遗传性疾病。因此，仅根据家族史不能可靠地将个体病例分类为“家族性”或“散发性”。作为遗传性AD的指标，aaa表型（或其他合适的标志物）似乎比明显的家族聚集程度更可靠。
