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 beta-amyloid (A beta) 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 A beta 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 A beta were incubated over a solid template prepared by immobilizing A beta 42 oligomers. The influence of Zn2+, Cu2+, and Fe3+ on A beta 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 A beta 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 A beta peptides or its aggregates.