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 transpo rt protein apolipoprotein E (apoE) are intimately associated with the 42-amino-acid beta-peptide (A beta) in the filamentous amyloid deposit s of Alzheimer's disease(1-3). We report here that these two amyloid-a ssociated proteins serve a strong stimulatory role in the polymerizati on of A beta into amyloid filaments. Addition of either alpha(1)-antic hymotrypsin or apoE to the A beta peptide promoted a 10- to 20-fold in crease in filament formation, with apoE-4, the isoform recently linked to the development of late-onset Alzheimer's disease, showing the hig hest catalytic activity. These and other experiments suggest that Alzh eimer amyloid deposits arise when A beta is induced to form filaments by amyloid-promoting factors (pathological chaperones) expressed in ce rtain brain regions.