Evidence that the β-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of Aβ by zinc

Abstract

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 ..