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Oral Zinc Reduces Amyloid Burden in Tg2576 Mice.

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.

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    Source

    Pub Type(s)

    JOURNAL ARTICLE

    Language

    ENG

    PubMed ID

    24595193

    Citation

    TY - JOUR T1 - Oral Zinc Reduces Amyloid Burden in Tg2576 Mice. A1 - Harris,Christopher J, AU - Voss,Kellen, AU - Murchison,Charles, AU - Ralle,Martina, AU - Frahler,Kate, AU - Carter,Raina, AU - Rhoads,Allison, AU - Lind,Betty, AU - Robinson,Emily, AU - Quinn,Joseph F, Y1 - 2014/3/4/ PY - 2014/3/6/entrez PY - 2014/3/7/pubmed PY - 2014/3/7/medline KW - Alzheimer's disease KW - amyloid-β protein KW - copper KW - transgenic mice SP - EP - JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/24595193/full_citation L2 - http://iospress.metapress.com/openurl.asp?genre=article&id=doi:10.3233/JAD-131703 ER -