Oral zinc reduces amyloid burden in Tg2576 mice

Christopher J. Harris, Kellen Voss, Charles Murchison, Martina Ralle, Kate Frahler, Raina Carter, Allison Rhoads, Betty Lind, Emily Robinson, Joseph F. Quinn

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)179-192
Number of pages14
JournalJournal of Alzheimer's Disease
Volume41
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Alzheimer's disease
  • amyloid-β protein
  • copper
  • transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Harris, C. J., Voss, K., Murchison, C., Ralle, M., Frahler, K., Carter, R., Rhoads, A., Lind, B., Robinson, E., & Quinn, J. F. (2014). Oral zinc reduces amyloid burden in Tg2576 mice. Journal of Alzheimer's Disease, 41(1), 179-192. https://doi.org/10.3233/JAD-131703