View article

Aβ 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 Aβ in vitro, and Cu²⁺ interaction with Aβ promotes its neurotoxicity, correlating with metal reduction and the cell-free generation of H₂O₂ (Aβ1–42 > Aβ1–40 > ratAβ1–40). Because Zn²⁺ is redox-inert, we studied the possibility that it may play an inhibitory role in H₂O₂-mediated Aβ 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 Aβ1–42, correlating with the effect of Zn²⁺ in suppressing Cu²⁺-dependent H₂O₂formation from Aβ1–42. Since plaques contain exceptionally high concentrations of Zn²⁺, we examined the relationship between oxidation (8-OH guanosine) levels in …