A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse model of Alzheimer's disease.

There is increasing evidence for the crucial role of metals in the pathology of Alzheimer's disease. Both the aggregation and neurotoxicity of amyloid-ß are dependent on the presence of copper. This study investigated the ability of the copper-complexing drug tetrathiomolybdate to reduce amyloid-ß pathology and spatial memory impairment in both a prevention and a treatment paradigm in the Tg2576 mouse model of Alzheimer's disease. Tetrathiomolybdate treatment lowered brain copper and reduced amyloid-ß levels in the prevention paradigm, but not in the treatment paradigm. Our data suggests that controlled lowering of systemic copper may achieve anti-amyloid effects if initiated early in the disease process.