The DOI matches its Crossref record; 97 of the 97 references it cites were found in a registry or an index.
Dramatic Aggregation of Alzheimer Aβ by Cu(II) Is Induced by Conditions Representing Physiological Acidosis
Open accessAbstract
The cortical deposition of Abeta is an event that occurs in Alzheimer's disease, Down's syndrome, head injury, and normal aging. Previously, in appraising the effects of different neurochemical factors that impact upon the solubility of Abeta, we observed that Zn2+ was the predominant bioessential metal to induce the aggregation of soluble Abeta at pH 7.4 in vitro and that this reaction is totally reversible with chelation. We now report that unlike other biometals tested at maximal biological concentrations, marked Cu2+-induced aggregation of Abeta1-40 emerged as the solution pH was lowered from 7.4 to 6.8 and that the reaction was completely reversible with either chelation or alkalinization. This interaction was comparable to the pH-dependent effect of Cu2+ on insulin aggregation but was not seen for aprotinin or albumin. Abeta1-40 bound three to four Cu2+ ions when precipitated at pH 7.0. Rapid, pH-sensitive aggregation occurred at low nanomolar concentrations of both Abeta1-40 and Abeta1-42 with submicromolar concentrations of Cu2+. Unlike Abeta1-40, Abeta1-42 was precipitated by submicromolar Cu2+ concentrations at pH 7.4. Rat Abeta1-40 and histidine-modified human Abeta1-40 were not aggregated by Zn2+, Cu2+, or Fe3+, indicating that histidine residues are essential for metal-mediated Abeta assembly. These results indicate that H+-induced conformational changes unmask a metal-binding site on Abeta that mediates reversible assembly of the peptide. Since a mildly acidic e…
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“For example, it was shown that that metal ions promote Aβ aggregation,16,17 as well as formation of reactive oxygen species (ROS) and lead to oxidative stress.18–20”
From The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity (2013) · cites this paper as [17]
In the citing paper
“However, the role of metal ions in Aβ42 aggregation still remains unclear and only few reports are available in the literature.37–41”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [37]
In the citing paper
“This is in contrast with a large number of reports showing the aggregation-promoting effect of metal ions on the Aβ peptide.23–27,29–32,37,38”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [37]
In the citing paper
“These metal ions have been shown to affect Aβ aggregation, as well as lead to the formation of reactive oxygen species (ROS).12−16”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [13]
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Cited by
Sorted by citations
Neurodegenerative diseases and oxidative stress
Barnham, K. J., Masters, C. L., & Bush, A. I. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1330 · Cited by 3,683
Self-citationThe neurobiology of zinc in health and disease
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Self-citationThe metallobiology of Alzheimer's disease
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Self-citation
Metadata
- Authors
- Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M. E., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., & Bush, A. I.
- Affiliations
- Harvard University (US)
- Corresponding author
- Bush, Ashley I.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-05
- Volume
- 273
- Issue
- 21
- Pages
- 12817-12826
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2018333394
- Cited by
- 1,009
- References
- 97
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 12 · 2023: 16 · 2022: 14 · 2021: 22 · 2020: 26 · 2019: 28 · 2018: 26 · 2017: 33 · 2016: 24 · 2015: 40 · 2014: 38 · 2013: 39 · 2012: 59
- FWCI
- 20.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (1R29AG1268601)
- National Cancer Institute
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- amyloid-beta aggregation, copper(II), acidosis, pH-dependent aggregation, Alzheimer's disease, Aβ40, amyloid-beta 42, zinc, histidine residues, metal ion binding, amyloid plaques, metal chelation, inflammation, neurodegeneration
- MeSH terms
- Acidosis, Alzheimer Disease, Animals, Copper, Humans, Hydrogen-Ion Concentration, Peptide Fragments, Protein Binding, Zinc, Amyloid beta-Peptides, Rats
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