Characterization of copper interactions with Alzheimer amyloid β peptides: Identification of an attomolar-affinity copper binding site on amyloid β1-42

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..