A Cu-amyloid beta complex activating Fenton chemistry in Alzheimer's disease: Learning with multiple first-principles simulations

Amyloid beta-peptides form complexes with copper, both in vitro and in vivo, relatively soluble in water as oligomers and active as catalysts for oxidation of organic substrates by hydrogen peroxide, a species always present in cells and in their aerobic environment. All these species are present in the synapse, thus making a connection between the amyloid cascade hypothesis and the oxidative damages by reactive oxygen species in neurons, when pathological dishomeostasis of amyloid peptides and metal ions occur. In order to understand the structural features of these toxic complexes, we built several models of Cu-Abeta peptides in monomeric and dimeric forms and we found, performing multiple first-principles molecular dynamics simulations, that Cu-induced dimers are more active than monomers in converting hydrogen peroxide into aggressive hydroxyl radicals.