Dual role of Cu2+ ions on the aggregation and degradation of soluble Aβ oligomers and protofibrils investigated by fluorescence spectroscopy and AFM

The neuropathological character of copper(II) ions (Cu2+) upon interaction with soluble human amyloid-beta(1-42) that subsequently generates senile plaques and/or reactive oxygen species (ROS) is considered as one of the very important features of Alzheimer's disease. The present study carried out by using fluorescence spectroscopy and atomic-force microscopy (AFM) indeed confirms the dual role played by Cu2+, namely as mediator of protein aggregation and as generator of ROS leading to irreversible protein alteration, which most likely involve two distinct copper-binding sites. The AFM investigations clearly evidence the copper-induced aggregation of A beta oligomers and protofibrils, while comparative fluorescence measurements with copper and zinc reveals the crucial involvement of redox-active copper in the generation of AA-cross-linked structures. (c) 2012 Elsevier Inc. All rights reserved.