Cited by 871Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments

Ma, Jianyi, Yee, Ann, Brewer, H. Bryan, Das, Saumya, Potter, Huntington·1994·Nature

Abstract

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.

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Crossref · 10.1038/372092a0

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Authors
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H.
Affiliations
  • Harvard University (US)
  • National Institutes of Health (US)
Venue
Nature
Published
1994-11
Volume
372
Issue
6501
Pages
92-94
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2021333248
Cited by
871
References
29
Citations by year
2026: 3 · 2025: 6 · 2024: 8 · 2023: 5 · 2022: 20 · 2021: 17 · 2020: 21 · 2019: 16 · 2018: 13 · 2017: 20 · 2016: 17 · 2015: 12 · 2014: 17 · 2013: 13 · 2012: 18
FWCI
47.73
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
alpha-1-antichymotrypsin, apolipoprotein E, amyloid-beta, Alzheimer's disease, APOE isoforms, APOE ε4, protease inhibitors, lipid transfer proteins, amyloidosis
MeSH terms
alpha 1-Antichymotrypsin, Alzheimer Disease, Apolipoproteins E, Biopolymers, Humans, Peptide Fragments, Amyloid beta-Peptides, Molecular Chaperones, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2, In Vitro Techniques

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