Copper(ii) and zinc(ii) dependent effects on Aβ42 aggregation: a CD, Th-T and SFM study

Abstract

Aβ aggregation is a central event in Alzheimer's disease (AD). In vitro evidence indicates that Aβ 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 Aβ aggregation process, their actual role in Aβ fibrillogenesis is still debated. In this work the effects of a molar excess of zinc(II) and/or copper(II) ions on the Aβ42 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 Aβ aggregates. These results further support the hypothesis that an altered distribution of metal ions in neurons might drive alternative Aβ aggregation pathways.