Jy. Ma et al., AMYLOID-ASSOCIATED PROTEINS ALPHA(1)-ANTICHYMOTRYPSIN AND APOLIPOPROTEIN-E PROMOTE ASSEMBLY OF ALZHEIMER BETA-PROTEIN INTO FILAMENTS, Nature, 372(6501), 1994, pp. 92-94
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.