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

Abstract

Zn(II) and Cu(II) precipitate Aβ in vitro into insoluble aggregates that are dissolved by metal chelators. We now report evidence that these biometals also mediate the deposition of Aβ amyloid in Alzheimer's disease, since the solubilization of Aβ 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 Aβ also required Mg(II) and Ca(II). The chelators were more effective in extracting Aβ 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.