Age-dependent expression of familial risk in Alzheimer's disease

There is growing evidence for genetic causes of Alzheimer's disease; therefore, consideration of its age at onset among genetically predisposed individuals is timely. The authors studied the onset of Alzheimer-like dementia in families of 79 probands ascertained clinically for the Bronx Veterans Administration/Mt. Sinai School of Medicine longitudinal studies of Alzheimer's disease. Analyses among their 379 first-degree relatives, living and decreased, suggested that 1) early onsets form a distribution that is distinct from that of later onsets, and thus, different causes or mechanisms may operate in early- and late-appearing disease; 2) age at onset varies as a familial characteristic; 3) with present population survival, only one third of the theoretical predisposition to Alzheimer's disease will become manifest during the lifetime of relatives at risk; and 4) a stable annual incidence of 1.5 per cent in the early ninth decade, reported by others, can be explained by the operation of a dominant gene with a population allele frequency of 0.13. The authors conclude that different (possibly genetic) causes of Alzheimer's disease may operate in different families or individuals, although much of its predisposition remains latent during the lifetime of those at risk.