Cu(II) Potentiation of Alzheimer Aβ Neurotoxicity

Abstract

Oxidative stress markers as well as high concentra- tions of copper are found in the vicinity of A amyloid deposits in Alzheimer’s disease. The neurotoxicity of A in cell culture has been linked to H2O2 generation by an unknown mechanism. We now report that Cu(II) mark- edly potentiates the neurotoxicity exhibited by A 1–42 > A 1–40 > in cell culture. The potentiation of toxicity is greatest for A > mouse/rat A 1–40, corresponding form H2O2 in cell-free assays and to exhibit amyloid pathology. The copper complex of A to their relative capacities to reduce Cu(II) to Cu(I), 1–42 has a highly positive formal reduction potential (500–550 mV ver- sus Ag/AgCl) characteristic of strongly reducing cupro- proteins. These findings suggest that certain redox ac- tive metal ions may be important in exacerbating and perhaps facilitating A -mediated oxidative damage in Alzheimer’s disease.