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. 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-anti-chymotrypsin 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.
Ma
J
J
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
Yee
A
A
Brewer
H B
HB
Das
S
S
Potter
H
H
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000648:ultrastructure; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000502:physiology*; D001704:Biopolymers / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018832:Molecular Chaperones / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D000514:alpha 1-Antichymotrypsin / Q000502:physiology*
D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D001704:Biopolymers; D018832:Molecular Chaperones; D010446:Peptide Fragments; D000514:alpha 1-Antichymotrypsin; C075222:amyloid beta-protein (1-42)