Alzheimer Aβ neurotoxicity: Promotion by antichymotrypsin, ApoE4; inhibition by Aβ-related peptides
Abstract
Two inflammation-associated proteins found in the Alzheimer amyloid deposits-alpha 1-antichymotrypsin (ACT) and apolipoprotein E4 (apoE4)-have been shown to be genetic risk factors for the development of Alzheimer's disease and to promote the polymerization of the A beta peptide into amyloid filaments in vitro. In the present study, we show that ACT and apoE4 increase the neurotoxicity of the A beta peptide in parallel with their promotion of filament formation. Preincubation of ACT or apoE4 with small A beta-related peptides, or of apoE4 with apoE2, abrogated their subsequent ability to promote both the formation and the neurotoxicity of A beta filaments. These results indicate that ACT and apoE4 may play a stimulatory role in the formation of neurotoxic amyloid in Alzheimer's disease, and that their amyloid promoting activity can be blocked by inhibitory peptides.
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ApoE directly interacts with Aβ, binding to its amino-acid residues 12-28, to exert its promoting effect on Aβ aggregation and brain deposition.
“To exert its promoting effect on Aβ aggregation and brain deposition, apoE directly interacts with Aβ, binding to its amino-acid residues 12–28 [11,12].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [11]
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- Authors
- Ma, J., Brewer, H. B., & Potter, H.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Potter, Huntington
- ORCID
- Potter, Huntington
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1996-09
- Volume
- 17
- Issue
- 5
- Pages
- 773-780
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2043656292
- Cited by
- 108
- References
- 8
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 2 · 2014: 2 · 2013: 3 · 2012: 7
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (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
- Alzheimer's disease, amyloid-beta, alpha-1-antichymotrypsin, APOE ε4, apolipoprotein E2, neurotoxicity, peptide inhibitors, inflammation, genetic risk factors
- MeSH terms
- alpha 1-Antichymotrypsin, Alzheimer Disease, Apolipoproteins E, Cells, Cultured, Glial Fibrillary Acidic Protein, Humans, Microscopy, Electron, Neurons, Neurotoxins, Peptides, Serine Proteinase Inhibitors, Amyloid beta-Peptides, Molecular Chaperones, Apolipoprotein E4
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