Influence of Multiple Metal Ions on β-Amyloid Aggregation and Dissociation on a Solid Surface

Abstract

Recently discovered evidences suggest that precipitation of Alzheimer's beta-amyloid (Abeta) peptide and the toxicity in Alzheimer's disease (AD) are caused by abnormal interactions with neocortical metal ions, especially Zn2+, Cu2+, and Fe3+. While many studies had focused on the role of a "single" metal ion and its interaction with Abeta peptides, such studies involving "multiple" metal ions have hardly been explored. Here, to explore the nature of codeposition of different metals, two or more metal ions along with Abeta were incubated over a solid template prepared by immobilizing Abeta42 oligomers. The influence of Zn2+,Cu2+, and Fe3+ on Abeta aggregation was investigated by two approaches: co-incubation and sequential addition. Our results using ex situ AFM, ThT-induced fluorescence, and FTIR spectroscopy indicated that the co-incubation of Cu2+, Zn2+, and Fe3+ significantly altered the morphology of aggregates. A concentration dependence study with mixed metal ions suggested that Zn2+ was required at much lower concentrations than Cu2+ to yield nonfibrillar amorphous Abeta deposits. In addition, sequential addition of Zn2+ or Cu2+ on fibrillar aggregates formed by Fe3+ demonstrated that Zn2+ and Cu2+ could possibly change the conformation of the aggregates induced by Fe3+. Our findings elucidate the coexistence of multiple metal ions through their interactions with Abeta peptides or its aggregates.