pH-dependent kinetics of copper ions binding to amyloid-β peptide

Interactions of amyloid-beta peptide (A beta) with Cu2+ are known to be pH-dependent and believed to play a crucial role in the neurotoxicity of Alzheimer's disease (AD). Some research has revealed that injured brains with lowered pH have higher risks of developing AD. However, reported experiments were performed under neutral or mildly acidic conditions, and no reports about the affinity of A beta-Cu2+ below pH 6.0. In this study, surface plasmon resonance (SPR) sensor with immobilized A beta was used to investigate the formation of A beta-Cu2+ complexes under acidic pH conditions. Dissociation constants were calculated and shown to be pH-dependent, ranging from 3.5 x 10(-8) M to 8.7 x 10(-3) M in the pH range from 7.0 to 4.0. The physiological significance of K-d was preliminarily investigated by monitoring the generation of OH+ in aerobic solutions containing A beta-Cu2+ and Cu2+. The results imply that acidic conditions could aggravate the oxidative stress in the presence of Cu2+, and the weak affinities of A beta-Cu2+ under mildly acidic pH of 5.0-6.0 could further enhance the oxidative damage. However, the oxidative stress effect of A beta is negligible due to the suppressed formation of A beta-Cu2+ below pH 5.0. This work is useful for the in-depth understanding of the role of A beta-Cu2+ in AD neuropathology. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.