AMYLOID-ASSOCIATED PROTEINS ALPHA(1)-ANTICHYMOTRYPSIN AND APOLIPOPROTEIN-E PROMOTE ASSEMBLY OF ALZHEIMER BETA-PROTEIN INTO FILAMENTS

THE protease inhibitor alpha(1)-antichymotrypsin and the lipid transport protein apolipoprotein E (apoE) are intimately associated with the 42-amino-acid beta-peptide (A beta) in the filamentous amyloid deposits of Alzheimer's disease(1-3). We report here that these two amyloid-associated proteins serve a strong stimulatory role in the polymerization of A beta into amyloid filaments. Addition of either alpha(1)-antichymotrypsin or apoE to the A beta peptide promoted a 10- to 20-fold increase in filament formation, with apoE-4, the isoform recently linked to the development of late-onset Alzheimer's disease, showing the highest catalytic activity. These and other experiments suggest that Alzheimer amyloid deposits arise when A beta is induced to form filaments by amyloid-promoting factors (pathological chaperones) expressed in certain brain regions.