Alzheimer's disease with and without coexisting Parkinson's disease changes: apolipoprotein E genotype and neuropathologic correlates.

The frequency of the apolipoprotein E (ApoE) epsilon 4 allele and its relationship with coexistent Parkinson's disease (PD) neuropathology in Alzheimer's disease (AD) have not been extensively explored. We determined ApoE genotype in 100 dementia patients with neuropathologically confirmed AD with and without concomitant Parkinson's disease (PD) changes (nigral degeneration and Lewy bodies at various sites). Fifty "AD+PD" patients were matched closely with 50 "pure AD" patients for age, sex, and duration of dementia. We found identical overrepresentation of the epsilon 4 allele in the two groups: 72% of the patients in each group had at least one ApoE epsilon 4 allele, compared with approximately 25% in the general population (p < 0.005) and in our institutional autopsy population (p < 0.001). Age at onset varied inversely with epsilon 4 allele dosage in men but not in women in both the AD and the AD+PD groups. As with amyloid deposition and plaque frequency in AD, we observed an association between epsilon 4 dosage and PD-related changes. Specifically, the severity of ubiquitin-positive neuritic change in CA2/3 of the hippocampus, but not the frequency of cortical Lewy bodies, varied significantly with epsilon 4 dosage in the AD+PD cases.