Copper(ii) and zinc(ii) dependent effects on A?42 aggregation: A CD, Th-T and SFM study

A? aggregation is a central event in Alzheimer's disease (AD). In vitro evidence indicates that A? aggregation and fibrillogenesis are significantly influenced by the employed experimental conditions. Indeed, although it is widely established that metal ions, such as copper and zinc, have significant effects on the A? aggregation process, their actual role in A? fibrillogenesis is still debated. In this work the effects of a molar excess of zinc(ii) and/or copper(ii) ions on the A?42 aggregation process and the morphology of the resultant aggregates have been compared in samples exhibiting different initial conformations. CD spectroscopy, Th-T-induced fluorescence and Scanning Force Microscopy (SFM) measurements indicated that both metal ions accelerate the aggregation process, yet significantly affect the morphology of aggregates. In particular, copper(ii) ions were the most effective in promoting non-fibrillar, amorphous A? aggregates. These results further support the hypothesis that an altered distribution of metal ions in neurons might drive alternative A? aggregation pathways. © 2013 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.