title: Studies in a large family with late-onset Alzheimer disease (LOAD).
abstract: A large 10-generation family with late-onset Alzheimer disease (LOAD) inherited as an autosomal dominant trait was evaluated historically, clinically, and genetically. The family origin was traced to a founder couple of French ancestry with approximately 3,000 descendants. Although the transmission of a genetic predisposition to LOAD is demonstrated through male individuals, a predominance of affected women is observed. Currently, 14 individuals, 12 of whom are women, are classified as affected with Alzheimer disease (AD). Among the affected, the age of onset ranged from 55 to 78 years. Genotyping of the apolipoprotein E (APOE) locus demonstrated that homozygotes for the E4 allele (APOE4) developed signs of AD in their late 60s, whereas affected heterozygotes presented with the disease in their 70s. A significantly higher APOE4 frequency was observed in affected family members than in those unaffected (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 those affected and can be attributed to an improved environment, including excellent care and management during the disabling phase of illness. Alternatively, it may be an example of the genetic heterogeneity in AD. Complete documentation of large families such as the one presented will facilitate the discovery of the multiple genetic factors involved in the pathogenesis of AD.
authors.affiliation: Department of Pathology and Laboratory Medicine, Christiana Care Health System, Newark, Delaware 19718-0001, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Martin
authors.forename: S E
authors.initials: SE
authors.lastname: Martin
authors.forename: L
authors.initials: L
authors.lastname: Edelsohn
authors.forename: D S
authors.initials: DS
authors.lastname: Borgaonkar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000523:psychology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D004185:Disability Evaluation; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant / Q000235:genetics; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000235:genetics; D015577:Geriatric Assessment; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016019:Survival Analysis
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005819:Genetic Markers