Apolipoprotein E sigma4 allele (ApoE sigma4) is associated with Alzheimer's disease (AD) in familial and sporadic cases, but the associations of ApoE sigma4 allele and vascular dementia (VD) and/or ischemic cerebrovascular disease (ICVD) are still controversial. To clarify the associations of ApoE polymorphism with AD, VD and ICVD in Japanese, we examined ApoE polymorphism in samples of 255 patients with AD, 87 patients with VD, and 123 patients with ICVD, as compared with 117 age-matched healthy control subjects (CTL). The frequency of the ApoE sigma4 allele was significantly higher in the VD group (0.21), the ICVD group (0.15) as well as in the AD group (0. 26) than in the CTL subjects (0.08). These findings suggest that the genotype of ApoE sigma4 is associated with not only AD but also VD and ICVD, and that ApoE sigma4 plays an important role in the development of dementia and ICVD.