Influence of multiple metal ions on beta-amyloid aggregation and dissociation on a solid surface

Abstract

Recently discovered evidences suggest that precipitation of Alzheimer's β-amyloid (Aβ) peptide and the toxicity in Alzheimer's disease (AD) are caused by abnormal interactions with neocortical metal ions, especially Zn 2+, Cu 2+, and Fe 3+. While many studies had focused on the role of a "single" metal ion and its interaction with Aβ 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 Aβ were incubated over a solid template prepared by immobilizing Aβ42 oligomers. The influence of Zn 2+, Cu 2+, and Fe 3+ on Aβ 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 Cu 2+, Zn 2+, and Fe 3+ significantly altered the morphology of aggregates. A concentration dependence study with mixed metal ions suggested that Zn 2+ was required at much lower concentrations than Cu 2+ to yield nonfibrillar amorphous Aβ deposits. In addition, sequential addition of Zn 2+ or Cu 2+ on fibrillar aggregates formed by Fe 3+ demonstrated that Zn 2+ and Cu2+ could possibly change the conformation of the aggregates induced by Fe 3+. Our findings elucidate the coexistence of multiple metal ions through their interactions with Aβ peptides or its aggregates.