CHARACTERIZATION OF STABLE COMPLEXES INVOLVING APOLIPOPROTEIN-E AND THE AMYLOID-BETA PEPTIDE IN ALZHEIMERS-DISEASE BRAIN

Genetic evidence suggests a role for apolipoprotein E (apoE) in Alzhei mer's disease (AD) amyloidogenesis. Here, amyloid-associated apoE from 32 AD patients was purified and characterized. We found that brain am yloid-associated apoE apparently exists not as free molecules but as c omplexes with polymers of the amyloid beta peptide (A beta). Brain A b eta-apoE complexes were detected irrespective of the apoE genotype, an d similar complexes could be mimicked in vitro. The fine structure of purified A beta-apoE complexes was fibrillar, and immunogold labeling revealed apoE immunoreactivity along the fibrils. Thus, we conclude th at A beta-apoE complexes are principal components of AD-associated bra in amyloid and that the data presented here support a role for apoE in the pathogenesis of AD.