Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice

Inhibition of neocortical beta -amyloid (A beta) accumulation may be essent ial in an effective therapeutic intervention for Alzheimer's disease (AD). Cu and Zn are enriched in A beta deposits in AD, which are solubilized by C u/Zn-selective chelators in vitro. Here we report a 49% decrease in brain A beta deposition (-375 mug/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an anti biotic and bioavailable Cu/Zn chelator. This was accompanied by a modest in crease in soluble A beta (1.45% of total cerebral A beta); APP, synaptophys in, and GFAP levels were unaffected. General health and body weight paramet ers were significantly more stable in the treated animals. These results su pport targeting the interactions of Cu and Zn with A beta as a novel therap y for the prevention and treatment of AD.