Apolipoprotein (Apo E) was genotyped using a fluorescent PCR-RFLP assay in 187 patients with a probable or possible clinical diagnosis of sporadic Alzheimer's disease (AD) and in 166 autopsied patients with dementia (21 presenile AD, 70 senile AD, 18 Lewy body dementia (LBD), 38 AD with cerebrovascular disease (AD-CVD), 19 vascular dementia). The relative epsilon 4 allele frequency was 0.472 in LBD, 0.513 in AD-CVD, 0.405 in presenile AD, 0.364 in senile AD, and 0.079 in vascular dementia. The relative epsilon 2 allele frequency was 0.211 in vascular dementia, 0.083 in LBD, 0.047 in presenile AD, 0.100 in senile AD and 0.039 in AD with CVD. We infer that apo E is a major risk factor for structural phenotypes of dementia involving AD, alone or in conjunction with another pathology. In addition, the epsilon 2 allele is likely to represent a risk factor for vascular morbidity, as the relative epsilon 2 allele frequency was 0.211 in patients with vascular dementia compared with 0.144 in elderly controls.