STUDIES IN A LARGE FAMILY WITH LATE-ONSET ALZHEIMER-DISEASE (LOAD)

A large IO-generation family with late-onset Alzheimer disease (LOAD) inherited as an autosomal dominant trait was evaluated historically, c linically, and genetically. The family origin was traced to a founder couple of French ancestry with approximately 3,000 descendants. Althou gh the transmission of a genetic predisposition to LOAD is demonstrate d through male individuals, a predominance of affected women is observ ed. Currently, 14 individuals, 12 of whom are women, are classified as affected with Alzheimer disease (AD). Among the affected the age of o nset ranged from 55 to 78 years. Genotyping of the apolipoprotein E (A POE) locus demonstrated that homozygotes for the E4 allele (APOE4) dev eloped signs of AD in their late 60s, whereas affected heterozygotes p resented with the disease in their,70s. A significantly higher APOE4 f requency was observed in affected family members than in those unaffec ted (0.79 vs. 0.25, chi(2) = 9.919, p = 0.0016, df = 1). Survival for more than 15 years after diagnosed onset was observed in a number of t hose affected and can be attributed to an improved environment, includ ing excellent care and management during the disabling phase of illnes s. Alternatively, it may be an example of the genetic heterogeneity in AD. Complete documentation of large families such as the one presente d will facilitate the discovery of the multiple genetic factors involv ed in the pathogenesis AD.