Affiliations: [a] Portland Veterans Affairs Medical Center, P3 R\&D, Portland, OR, USA | [b] Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA | [c] Department of Pathology, Oregon Health and Sciences University, Portland, OR, USA | [d] Department of Biochemistry, Oregon Health and Sciences University, Portland, OR, USA | [e] Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Correspondence:
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Correspondence to: Joseph Quinn, MD, Oregon Health and Sciences University, Department of Neurology CR-131, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA. Tel.: +1 503 494 6976; Fax: +1 503 494 7499; E-mail: [email protected].
Note: [] Handling Associate Editor: Ashley Bush
Abstract: There is increasing evidence for the crucial role of metals in the pathology of Alzheimer's disease. Both the aggregation and neurotoxicity of amyloid-β are dependent on the presence of copper. This study investigated the ability of the copper-complexing drug tetrathiomolybdate to reduce amyloid-β 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-β 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.
