Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments
Abstract
THE protease inhibitor α,-antichymotrypsin and the lipid transport protein apolipoprotein E (apoE) are intimately associated with the 42-amino-acid β-peptide (Aβ) in the filamentous amyloid deposits of Alzheimer's disease1-3. We report here that these two amyloid-associated proteins serve a strong stimulatory role in the polymeri-zation of Aβ into amyloid filaments. Addition of either α,-anti-chymotrypsin or apoE to the Aβ 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 Aβ is induced to form filaments by amyloid-promoting factors (pathological chaperones) expressed in certain brain regions.
- Publication:
-
Nature
- Pub Date:
- November 1994
- DOI:
- 10.1038/372092a0
- Bibcode:
- 1994Natur.372...92M