Current Status of Metals as Therapeutic Targets in Alzheimer's Disease
There is accumulating evidence that interactions between -amyloid and copper, iron, and zinc are associated with the pathophysiology of Alzheimer’s disease (AD). A significant dyshomeostasis of copper, iron, and zinc has been detected, and the mismanagement of these metals induces -amyloid precipitation and neurotoxicity. Chelating agents offer a potential therapeutic solution to the neurotoxicity induced by copper and iron dyshomeostasis. Currently, the copper and zinc chelating agent clioquinol represents a potential therapeutic route that may not only inhibit -amyloid neurotoxicity, but may also reverse the accumulation of neocortical -amyloid. A Phase II doubleblind clinical trial of clioquinol with B12 supplementation will be published soon, and the results are promising. This article summarizes the role of transition metals in amyloidgenesis and reviews the potential promise of chelation therapy as a treatment for AD. J Am Geriatr Soc 51:1143–1148, 2003.

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