Characterization of Copper Interactions with Alzheimer Amyloid β Peptides: Identification of an Attomolar‐Affinity Copper Binding Site on Amyloid β1‐42

Atwood, Craig S.; Scarpa, Richard C.; Huang, Xudong; Moir, Robert D.; Jones, Walton D.; Fairlie, David P.; Tanzi, Rudolph E.; Bush, Ashley I.

doi:10.1046/j.1471-4159.2000.0751219.x

Cited by 641Alzheimer's disease research and treatmentsTrace Elements in HealthDementia and Cognitive Impairment Research

Characterization of Copper Interactions with Alzheimer Amyloid β Peptides: Identification of an Attomolar‐Affinity Copper Binding Site on Amyloid β1‐42

Atwood, Craig S., Scarpa, Richard C., Huang, Xudong, Moir, Robert D., Jones, Walton D., Fairlie, David P., Tanzi, Rudolph E., Bush, Ashley I.·2000·Journal of Neurochemistry

DOI 10.1046/j.1471-4159.2000.0751219.x

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Abstract

Abstract: Cu and Zn have been shown to accumulate in the brains of Alzheimer's disease patients. We have previously reported that Cu 2+ and Zn 2+ bind amyloid β (Aβ), explaining their enrichment in plaque pathology. Here we detail the stoichiometries and binding affinities of multiple cooperative Cu 2+‐binding sites on synthetic Aβ1‐40 and Aβ1‐42. We have developed a ligand displacement technique (competitive metal capture analysis) that uses metal‐chelator complexes to evaluate metal ion binding to Aβ, a notoriously self‐aggregating peptide. This analysis indicated that there is a very‐high‐affinity Cu 2+‐binding site on Aβ1‐42 (log Kapp = 17.2) that mediates peptide precipitation and that the tendency of this peptide to self‐aggregate in aqueous solutions is due to the presence of trace Cu 2+ contamination (customarily ∼0.1 μ M). In contrast, Aβ1‐40 has much lower affinity for Cu 2+ at this site (estimated log Kapp = 10.3), explaining why this peptide is less self‐aggregating. The greater Cu 2+‐binding affinity of Aβ1‐42 compared with Aβ1‐40 is associated with significantly diminished negative cooperativity. The role of trace metal contamination in inducing Aβ precipitation was confirmed by the demonstration that Aβ peptide (10 μ M) remained soluble for 5 days only in the presence of high‐affinity Cu 2+‐selective chelators.

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The role of metal ions in Aβ42 aggregation remains unclear and only few reports are available in the literature.
“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 Aβ<sub>42</sub>Peptide (2012) · cites this paper as [38]

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Authors: Atwood, C. S., Scarpa, R. C., Huang, X., Moir, R. D., Jones, W. D., Fairlie, D. P., Tanzi, R. E., & Bush, A. I.
Affiliations: Harvard University (US)
ORCID: Atwood, Craig S.
Huang, Xudong
Moir, Robert D.
Jones, Walton D.
Fairlie, David P.
Tanzi, Rudolph E.
Bush, Ashley I.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2000-09
Volume: 75
Issue: 3
Pages: 1219-1233
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1046/j.1471-4159.2000.0751219.x
OpenAlex: W1966618264
Cited by: 641
References: 6
Citations by year: 2026: 11 · 2025: 13 · 2024: 15 · 2023: 18 · 2022: 25 · 2021: 13 · 2020: 15 · 2019: 21 · 2018: 18 · 2017: 12 · 2016: 22 · 2015: 18 · 2014: 16 · 2013: 20 · 2012: 41
FWCI: 14.01
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2943 d)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r29ag012686-01a1)
National Institute on Aging (R29AG12686)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: copper binding, amyloid-beta, Alzheimer's disease, Aβ40, amyloid-beta 42, metal-peptide interactions, metal chelators, peptide self-aggregation, binding stoichiometry, negative cooperativity, trace metal contamination
MeSH terms: Animals, Binding Sites, Chelating Agents, Copper, Dogs, Humans, Kinetics, Peptide Fragments, Regression Analysis, Serum Albumin, Zinc, Amyloid beta-Peptides

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Characterization of Copper Interactions with Alzheimer Amyloid β Peptides: Identification of an Attomolar‐Affinity Copper Binding Site on Amyloid β1‐42

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