The cause of Alzheimer's disease (AD) is closely related to the aggregation of a normal protein, β-amyloid (Aβ), within the neocortex. Recently, evidence has been gathered to suggest that Aβ precipitation and toxicity in AD are caused by abnormal interactions with neocortical metal ions, especially Zn, Cu and Fe. However, Aβ might also participate in normal metal-ion homeostasis. An inevitable, age-dependent rise in brain Cu and Fe might hypermetallate the Aβ peptide, causing the catalysis of H₂O₂ production that mediates the toxicity and auto-oxidation of Aβ. The greater incidence of AD in females could be due to greater constitutive activity of the synaptic Zn transporter ZnT3, and attenuated binding of metal ions to the rodent homologue of Aβ might explain why these animals are spared Alzheimer's pathology. Compounds that interdict metal-ion binding to Aβ dissolve brain deposits in vitro and one such compound, clioquinol, inhibits Aβ deposition in the Tg2576 mouse model for AD and could be useful clinically. These insights could also apply to other degenerative disorders in which metal-ion–protein interactions have been implicated.