Cellular and Molecular Neurobiology

, Volume 29, Issue 5, pp 757–767 | Cite as

Chronic Exposure to High Levels of Zinc or Copper has Little Effect on Brain Metal Homeostasis or Aβ Accumulation in Transgenic APP-C100 Mice

  • Christa J. Maynard
  • Roberto Cappai
  • Irene Volitakis
  • Katrina M. Laughton
  • Colin L. Masters
  • Ashley I. Bush
  • Qiao-Xin Li
Original paper


Aberrant metal homeostasis may enhance the formation of reactive oxygen species and Aβ oligomerization and may therefore be a contributing factor in Alzheimer’s disease. This study investigated the effect of chronic high intake of dietary Zn or Cu on brain metal levels and the accumulation and solubility of Aβ in vivo, using a transgenic mouse model that over expresses the C-terminal containing Aβ fragment of human amyloid precursor protein but does not develop amyloid deposits. Exposure to chronic high Zn or Cu in the drinking water resulted in only slight elevations of the respective metals in the brain. Total Aβ levels were unchanged although soluble Aβ levels were slightly decreased, without visible plaque formation, enhanced gliosis, antioxidant upregulation or neuronal loss. This study indicates that brain metal levels are only marginally altered by long term oral exposure to extremely high Cu or Zn levels, and that this does not induce Aβ-amyloid formation in human Aβ expressing, amyloid-free mice, although this is sufficient to modulate Aβ solubility in vivo.


Alzheimer’s disease Amyloid-beta peptide Copper Zinc APP-C100 



Alzheimer’s disease

Amyloid β-peptide


Amyloid precursor protein


The C-terminal fragment of amyloid precursor protein containing the Aβ peptide, also referred to as βCTF


Glial fibrillary acidic protein




Cu/Zn superoxide dismutase


Sodium dodecyl sulfate


Phosphate buffer saline



We thank Ms. Tina Cardamone for assisting with immunohistochemistry. This work was supported in part by grants from the National Health and Medical Research Council of Australia.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Christa J. Maynard
    • 1
    • 2
    • 4
  • Roberto Cappai
    • 1
    • 2
  • Irene Volitakis
    • 2
  • Katrina M. Laughton
    • 1
    • 2
  • Colin L. Masters
    • 1
    • 2
  • Ashley I. Bush
    • 1
    • 2
    • 3
  • Qiao-Xin Li
    • 1
    • 2
  1. 1.Department of PathologyThe University of MelbourneMelbourneAustralia
  2. 2.Oxidation Disorders Laboratory and Alzheimer’s Disease DivisionMental Health Research Institute of VictoriaParkvilleAustralia
  3. 3.Laboratory for Oxidation Biology, Genetics and Aging Research Unit, and Department of Psychiatry, Harvard Medical SchoolMassachusetts General HospitalCharlestownUSA
  4. 4.Department of Cell and Molecular Biology, The Medical Nobel InstituteKarolinska InstitutetStockholmSweden

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