Brains from 21 patients with Alzheimer's disease (AD), nine with diffuse Lewy body disease (DLBD), six with progressive supranuclear palsy (PSP) and five with Parkinson's disease (PD) as well as 20 normal subjects were examined to detect apolipoprotein E (ApoE) by immunohistochemistry and immunoblotting. ApoE antigenicity was optimally preserved in Bouin-fixed tissues compared with those fixed in neutral-buffered formalin, 70% ethanol or denatured by microwave energy. ApoE immunoreactivity was prominent in senile plaques and in intra- and extra-neuronal tangles, as well as in a diverse neurones and their processes and astroglial cells. Notably, tangles in PSP and Lewy bodies in PD and DLBD were both devoid of ApoE immunoreactivity. Western blots of cerebral cortex revealed an immunoreactive ApoE band with mol. wt of 34 kDa. Our results suggest that ApoE is not a crucial factor in the development of neuronal inclusions in DLBD, PSP and PD.