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Abeta binds Zn2+, Cu2+, and Fe3+ in vitro, and these metals are markedly elevated in the neocortex and especially enriched in amyloid plaque deposits of individuals with Alzheimer's disease (AD). Zn2+ precipitates Abeta in vitro, and Cu2+ interaction with Abeta promotes its neurotoxicity, correlating with metal reduction and the cell-free generation of H2O2 (Abeta1-42 > Abeta1-40 > ratAbeta1-40). Because Zn2+ is redox-inert, we studied the possibility that it may play an inhibitory role in H2O2-mediated Abeta toxicity. In competition to the cytotoxic potentiation caused by coincubation with Cu2+, Zn2+ rescued primary cortical and human embryonic kidney 293 cells that were exposed to Abeta1-42, correlating with the effect of Zn2+ in suppressing Cu2+-dependent H2O2 formation from Abeta1-42. Since plaques contain exceptionally high concentrations of Zn2+, we examined the relationship between oxidation (8 …