Familial aggregation in Alzheimer dementia--II. Clinical genetic implications of age-dependent onset

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.