INFLUENCE OF APOLIPOPROTEIN-E GENOTYPE ON SENILE DEMENTIA OF THE ALZHEIMER AND LEWY BODY TYPES - SIGNIFICANCE FOR ETIOLOGIC THEORIES OF ALZHEIMERS-DISEASE

Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the diseas e and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body typ e (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary co mplications. The epsilon 4 allele frequency was increased in SDLT (0.3 65) and AD (0.328) as compared with controls (0.147), PD (0.098), or H untington's chorea (0.171). Coronary disease and vascular dementia wer e associated with marginally higher epsilon 4 allele frequencies than in controls. In PD, amyloid beta-protein accumulated to a greater exte nt in those cases Possessing an epsilon 4 allele than in those without . Those PD cases with dementia were not distinguished from either cont rols or PD cases without dementia, whether tested biochemically or by apolipoprotein E genotype. It is the comparison of the results in AD a nd SDLT that yielded the most significant findings. There was a 1.8-fo ld excess of amyloid beta-protein in AD as compared with controls, and the levels in SDLT were intermediate between those in AD and controls . In contrast, AD was discriminated from both controls and SDLT by the substantial accumulation of paired helical filament tau and phosphory lated tau (both increased more than 20-fold as compared with controls) . SDLT was nevertheless characterized by an increased epsilon 4 allele frequency in the absence of significant tau pathology (at least 10-fo ld less than that in AD). These findings indicate that talc processing is more specifically associated with AD than is amyloid beta-protein accumulation and that presence of the epsilon 4 allele is not an etiol ogical factor that accounts for tau pathology.