We ascertained 56 related cases with early onset familial Alzheimer's disease (EOFAD; mean age of onset < 65 years) and 10 related cases with late onset familial Alzheimer's disease (LOFAD; mean age of onset > or = 65 years) through a questionnaire administered to neuro-psychiatric and medical school hospitals in Japan and through a review of cases in Japanese literature. Mean age of onset and death (+/- S.D.) of EOFAD were 43.4 +/- 8.6 years (n = 94) and 51.1 +/- 10.5 years (n = 85), respectively. Distributions of the age-onset were relatively constant within a family but significantly different between families. Our result may suggest that clinical differences between families represent genetic heterogeneity at the molecular level. Six out of 32 related cases of with EOFAD showed the 717 Val-->Ile mutation of beta/A4 amyloid precursor protein (APP) gene. This result suggests that the frequency of this mutation in Japanese population is higher than in Caucasian and allelic the existenced heterogeneity, in Japanese EOFAD.