Metal ions differentially influence the aggregation and deposition of Alzheimer's beta-amyloid on a solid template

Abstract

The abnormal deposition and aggregation of β-amyloid (Aβ) on brain tissues are considered to be one of the characteristic neuropathological features of Alzheimer's disease (AD). Environmental conditions such as metal ions, pH, and cell membranes are associated with Aβ deposition and plaque formation. According to the amyloid cascade hypothesis of AD, the deposition of Aβ oligomers as diffuse plaques in vivo is an important earliest event, leading to the formation of fibrillar amyloid plaques by the further accumulation of soluble Aβ under certain environmental conditions. In order to characterize the effect of metal ions on amyloid deposition and plaque growth on a solid surface, we prepared a synthetic template by immobilizing Aβ oligomers onto a N-hydroxysuccinimide ester-activated solid surface. According to our study using ex situ atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), and thioflavin T (ThT) fluorescence spectroscopy, Cu 2+ and Zn 2+ ions accelerated both Aβ40 and Aβ42 deposition but resulted only in the formation of "amorphous" aggregates. In contrast, Fe 3+ induced the deposition of "fibrillar" amyloid plaques at neutral pH. Under mildly acidic environments, the formation of fibrillar amyloid plaques was not induced by any metal ion tested in this work. Using secondary ion mass spectroscopy (SIMS) analysis, we found that binding Cu ions to Aβ deposits on a solid template occurred by the possible reduction of Cu ions during the interaction of Aβ with Cu 2+. Our results may provide insights into the role of metal ions on the formation of fibrillar or amorphous amyloid plaques in AD.