The apolipoprotein E epsilon 4 allele in Parkinson's disease with Alzheimer lesions.

The association between the apolipoprotein E (ApoE) epsilon 4 allele and Parkinson's disease (PD) with coexistent dementia has remained controversial. We determined ApoE allele frequencies in 35 subjects with neuropathologically confirmed Lewy body Parkinsonism with and without concomitant Alzheimer lesions, 27 patients with Alzheimer's disease (AD), and 54 controls without neurodegenerative disease. We hypothesized that if AD lesions in PD evolve by the same pathomechanism as in "pure AD," the ApoE epsilon 4 allele frequency in PD with AD lesions (PD+AD) and pure AD should be similar. The frequency of the ApoE epsilon 4 allele differed significantly between PD+AD (13.3%) and AD cases (35.2%), but not between PD+AD and PD without AD pathology (12.5%) or controls (11.1%). We conclude that the ApoE epsilon 4 allele does not function as a risk factor which influences the development of AD lesions in PD. Our data suggest that Parkinson's disease with Alzheimer lesions and Alzheimer's disease with coexistent Parkinsonian features represent two distinct entities at both the clinicopathological and molecular genetic levels.