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.
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Ma, J., Yee, A., Brewer, H. et al. Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments. Nature 372, 92–94 (1994). https://doi.org/10.1038/372092a0
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DOI: https://doi.org/10.1038/372092a0
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