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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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  • Authors+Show Affiliations

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    Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

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    Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

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    Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

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    Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, USA.

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    Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

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    Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

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    Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

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    Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

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    Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, USA.

    Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR, USA Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

    Source

    MeSH

    Administration, Oral
    Alzheimer Disease
    Amyloid beta-Protein Precursor
    Amyloidosis
    Animals
    Body Weight
    Brain
    Ceruloplasmin
    Copper
    Disease Models, Animal
    Female
    Humans
    Maze Learning
    Mice, Inbred C57BL
    Mice, Transgenic
    Motor Activity
    Neuroprotective Agents
    Random Allocation
    Spatial Memory
    Zinc
    Zinc Acetate

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    24595193

    Citation

    * When formatting your citation, note that all book, journal, and database titles should be italicized* Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Oral zinc reduces amyloid burden in Tg2576 mice. AU - 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, PY - 2014/3/6/entrez PY - 2014/3/7/pubmed PY - 2015/1/30/medline KW - Alzheimer's disease KW - amyloid-β protein KW - copper KW - transgenic mice SP - 179 EP - 92 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 41 IS - 1 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 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-131703 DB - PRIME DP - Unbound Medicine ER -