To assess the significance of the association between apolipoprotein E (APOE) epsilon 4 allele and amyloid beta-peptide (A-beta) deposits in the brain, we performed APOE-genotyping and measured the density of A-beta deposits, neuritic plaques and neurofibrillary tangles in 27 cases from the Charles Foix clinico-pathological prospective study. We found an increased density of A-beta deposits in the three cases with the epsilon 3/epsilon 4 genotype as compared-with epsilon 3/epsilon 3 subjects. Surprisingly, one of the epsilon 3/epsilon 4 genotypes was a 88-year-old woman, with normal intellectual functions and very low densities of neuritic plaques and neurofibrillary tangles but very high densities of preamyloid diffuse deposits of A-beta. This observation contrasted with the expected association between Alzheimer's disease and APOE epsilon 4 allele.