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

Abstract

Interactions of amyloid-β peptide (Aβ) 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 Aβ−Cu2+ below pH6.0. In this study, surface plasmon resonance (SPR) sensor with immobilized Aβ was used to investigate the formation of Aβ−Cu2+ complexes under acidic pH conditions. Dissociation constants were calculated and shown to be pH-dependent, ranging from 3.5×10−8M to 8.7×10−3M in the pH range from 7.0 to 4.0. The physiological significance of Kd was preliminarily investigated by monitoring the generation of OH in aerobic solutions containing Aβ−Cu2+ and Cu2+. The results imply that acidic conditions could aggravate the oxidative stress in the presence of Cu2+, and the weak affinities of Aβ−Cu2+ under mildly acidic pH of 5.0–6.0 could further enhance the oxidative damage. However, the oxidative stress effect of Aβ is negligible due to the suppressed formation of Aβ−Cu2+ below pH5.0. This work is useful for the in-depth understanding of the role of Aβ−Cu2+ in AD neuropathology.