Expression of apolipoprotein E inhibits aggregation of the C-terminal fragments of beta-amyloid precursor protein.

An important role of apolipoprotein E in the amyloidogenesis of Alzheimer's disease is suggested by an accumulation of apolipoprotein E in beta-amyloid plaques and a genetic association between Alzheimer's disease and one of the allelic variants (APOE4) of apolipoprotein E. Overexpression of a C-terminal region of beta-amyloid precursor protein brings about aggregation of the C-terminal fragments in COS cells. This COS cell culture system was used to study effects of apolipoprotein E on aggregation of the C-terminal fragments. When both apolipoprotein E and the C-terminal fragments were overexpressed in COS cells, Western blot analyses revealed significant inhibition of aggregation of the C-terminal fragments. No significant differences between apolipoprotein E3 and E4 in the inhibitory activities were found by this method. Apolipoprotein E may inhibit formation of amyloid fibrils.