[Alzheimer's presenile dementia transmitted in an extended kindred]

Forty-three patients affected with Alzheimer's disease were identified in a kindred of Italian origin, emigrated in part to the U.S.A. and France. Thirteen were known by history, 21 by medical record, and 9 by personal examination, of whom 5 were confirmed histopathologically. The clinical picture was fairly uniform: the first symptom was memory loss beginning around age 40. Psychotic-like symptoms often followed, with rapid evolution into profound dementia, and death around age 50. Akinesia was prominent at a late stage, often with myoclonus. Grand mal seizures sometimes occurred, with occasional interictal spike and wave discharge; repetitive paroxystic periodic discharges were never recorded. A genealogical study, as far as possible free from line bias, has been conducted mainly by analysis of municipal records. 1 435 subjects in 10 generations, linked to affected subjects through ascent/descent or marriage, were listed in a computer file; the corresponding genealogical tree or selected part thereof are generated by computer. Application of Bayesian techniques to demographic data makes possible an estimation of disease probability in subjects for which no clinical data were available: such an estimate was confirmed by the later discovery of a living patient in descent of a subject with 0.7 estimated disease probability. No patient was found in descent from an inbred union known as such. Patients are the only transmitters. The sex ratio is not significantly different from 1. There is no detectable maternal effect. The segregation ratio, as calculated from extensively known sibships, lies in the range 0.65 to 0.89; the lower value itself is significatively higher than the 0.5 value expected in an autosomal dominant monogenic Mendelian transmission. An environment factor is ruled out by the diversity of locations and circumstances in kindred members. Such a kindred may represent an useful model for fundamental studies in Alzheimer's disease and senile dementia of the Alzheimer type.