The apolipoprotein E epsilon 4 allele is associated with increased neuritic plaques and cerebral amyloid angiopathy in Alzheimer's disease and Lewy body variant

Objective: To determine the relationship between apolipoprotein E (apoE) genotype and neuropathologic lesions in Alzheimer's disease (AD) and Lewy body variant (LBV). Design: Retrospective genetic-neuropathologic study of AD and LBV cases. The main neuropathologic outcome measures were modeled as a function of apoE genotype, neuropathologic diagnosis, and gender. Age at death and duration of symptom effects were controlled for by ANCOVA. Patients: One hundred twenty-seven cases with neuropathologically diagnosed AD (n = 84) or LBV (n = 43). Main outcome measures: Quantitative scores of neuritic plaques (NPs), neurofibrillary tangles (NFTs), cerebral amyloid angiopathy (CAA) severity, and CAA prevalence were averaged across four brain regions: midfrontal, inferior parietal, superior temporal, and hippocampal. Results: The apoE epsilon 4 allele was associated with increased NPs within both AD and LBV. The epsilon 4 allele was associated with an increased frequency of CAA in the AD and LBV groups combined and in LBV alone. While CAA severity and NFTs were increased in the epsilon 4/4 homozygous cases when AD and LBV were combined, there were no significant effects within AD or LBV alone. Conclusions: The apoE epsilon 4 allele is strongly associated with increased NPs, but not neocortical NFTs, in both AD and LBV.