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Abstract: Cu and Zn have been shown to accumulate in the brains of Alzheimer's disease patients. We have previously reported that Cu²⁺ and Zn²⁺ bind amyloid β (Aβ), explaining their enrichment in plaque pathology. Here we detail the stoichiometries and binding affinities of multiple cooperative Cu²⁺‐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 Cu²⁺‐binding site on Aβ1‐42 (log K_app = 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 Cu²⁺ contamination (customarily ∼0.1 μM). In contrast, Aβ1‐40 has much lower affinity for Cu²⁺ at this …