The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments
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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In the citing paper
“lipid-free apoE4 was found to facilitate Aβ fibrillization in vitro to a greater degree compared to apoE3 [(47, 48); see (39) for a review].”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [47]
In the citing paper
“ApoE has also been reported to promote A 𝛃 aggregation (5)”
From Therapeutic Idol reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice (2020) · cites this paper as [5]
In the citing paper
“As apoE co-deposits with Aβ in the amyloid plaques (13–15), we examined and found that the degree of co-localization between apoE and Aβ deposition appeared to decrease in the brains carrying APOE3-Jac variant compared to those from APOE3 (Fig. S1C–F).”
From APOE3 -Jacksonville (V236E) variant reduces self-aggregation and risk of dementia (2021) · cites this paper as [13]
In the citing paper
“In vitro, apoE and apoJ form stable complexes with A (11, 16 -20), alter the aggregation of various A peptides (21)(22)(23), and affect A neurotoxicity (24 -27).”
From Apolipoprotein E Receptors Mediate the Effects of β-Amyloid on Astrocyte Cultures (2000) · cites this paper as [21]
In the citing paper
“Together these data expand previous studies in mouse models of Aβ aggregation suggesting a pathogenic role for C4b and Serpina3n23,24,44,45, as well as genetic studies linking the human homologue SERPINA3 to AD risk46”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [45]
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Metadata
- 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
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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