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

Abstract

Inhibition of neocortical β-amyloid (Aβ) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD). Cu and Zn are enriched in Aβ deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro. Here we report a 49% decrease in brain Aβ deposition (-375 μg/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator. This was accompanied by a modest increase in soluble Aβ (1.45% of total cerebral Aβ); APP, synaptophysin, and GFAP levels were unaffected. General health and body weight parameters were significantly more stable in the treated ..