Nature, Vol.372, No.6501, 92-94, 1994
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.
Keywords:INHIBITOR ALPHA-1-ANTICHYMOTRYPSIN;TYPE-4 ALLELE;DISEASE;PEPTIDE;DEPOSITS;BINDING;INVITRO;METABOLISM;FIBRILS;PLAQUE