Aqueous dissolution of Alzheimer's disease Aβ amyloid deposits by biometal depletion

Zn(II) and Cu(II) precipitate AP in vitro into insoluble aggregates that are dissolved by metal chelators. We now report evidence that these biometals also mediate the deposition of AP amyloid in Alzheimer's disease, since the solubilization of AP from post-mortem brain tissue was significantly increased by the presence of chelators, EGTA, N,N,N',N'-tetrakis(2-pyridyl-methyl) ethylene diamine, and bathocuproine. Efficient extraction of A beta also required Mg(II) and Ca(II), The chelators were more effective in extracting AP from Alzheimer's disease brain tissue than age-matched controls, suggesting that metal ions differentiate the chemical architecture of amyloid in Alzheimer's disease. Agents that specifically chelate copper and zinc ions but preserve Mg(II) and Ca(II) may be of therapeutic value in Alzheimer's disease.