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A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse model of Alzheimer's disease.

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.

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    • Grapherence [↓12 ↑27]

    Authors+Show Affiliations

    Quinn JF
    ,

    Portland Veterans Affairs Medical Center, P3 R&D, Portland, OR, USA. quinnj@ohsu.edu

    Harris CJ
    ,
    Cobb KE
    ,
    Domes C
    ,
    Ralle M
    ,
    Brewer G
    ,
    Wadsworth TL

    Source

    MeSH

    Alzheimer Disease
    Amyloid beta-Peptides
    Analysis of Variance
    Animals
    Blotting, Western
    Cerebral Cortex
    Ceruloplasmin
    Chelating Agents
    Copper
    Enzyme-Linked Immunosorbent Assay
    Hippocampus
    Immunohistochemistry
    Maze Learning
    Memory Disorders
    Mice
    Mice, Transgenic
    Molybdenum
    Random Allocation

    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

    20693639

    Citation

    Quinn, Joseph F., et al. "A Copper-lowering Strategy Attenuates Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 21, no. 3, 2010, pp. 903-14.
    Quinn JF, Harris CJ, Cobb KE, et al. A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2010;21(3):903-14.
    Quinn, J. F., Harris, C. J., Cobb, K. E., Domes, C., Ralle, M., Brewer, G., & Wadsworth, T. L. (2010). A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse model of Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 21(3), pp. 903-14. doi:10.3233/JAD-2010-100408.
    Quinn JF, et al. A Copper-lowering Strategy Attenuates Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2010;21(3):903-14. PubMed PMID: 20693639.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse model of Alzheimer's disease. AU - Quinn,Joseph F, AU - Harris,Christopher J, AU - Cobb,Katherine E, AU - Domes,Christopher, AU - Ralle,Martina, AU - Brewer,George, AU - Wadsworth,Teri L, PY - 2010/8/10/entrez PY - 2010/8/10/pubmed PY - 2011/1/19/medline SP - 903 EP - 14 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 21 IS - 3 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/20693639/A_copper_lowering_strategy_attenuates_amyloid_pathology_in_a_transgenic_mouse_model_of_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2010-100408 DB - PRIME DP - Unbound Medicine ER -