Affiliations: [a] Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR, USA | [b] Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA | [c] Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, USA
Correspondence:
[*]
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: quinnj@ohsu.edu.
Abstract: The aggregation of amyloid-β in Alzheimer's disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid-β in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid-β in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid-β aggregation.
