title: Elevated copper in the amyloid plaques and iron in the cortex are observed in mouse models of Alzheimer's disease that exhibit neurodegeneration.
abstract: BACKGROUND
  In Alzheimer's disease (AD), alterations in metal homeostasis, including the accumulation of metal ions in the plaques and an increase of iron in the cortex, have been well documented but the mechanisms involved are poorly understood.
  
  
  OBJECTIVE
  In this study, we compared the metal content in the plaques and the iron speciation in the cortex of three mouse models, two of which show neurodegeneration (5xFAD and Tg-SwDI/NOS2-/-(CVN) and one that shows very little neurodegeneration (PSAPP).
  
  
  METHODS
  The Fe, Cu, and Zn contents and speciation were determined using synchrotron X-ray fluorescence microscopy (XFM) and X-ray absorption spectroscopy (XAS), respectively.
  
  
  RESULTS
  In the mouse models with reported significant neurodegeneration, we found that plaques contained ~25% more copper compared to the PSAPP mice. The iron content in the cortex increased at the late stage of the disease in all mouse models, but iron speciation remains unchanged.
  
  
  CONCLUSIONS
  The elevation of copper in the plaques and iron in the cortex is associated with AD severity, suggesting that these redox-active metal ions may be inducing oxidative damage and directly influencing neurodegeneration.
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook NY, USA.
authors.forename: Megan W
authors.initials: MW
authors.lastname: Bourassa
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Andreana C
authors.initials: AC
authors.lastname: Leskovjan
authors.affiliation: Photon Sciences Directorate, Brookhaven National Laboratory, Upton, NY, USA.
authors.forename: Ryan V
authors.initials: RV
authors.lastname: Tappero
authors.affiliation: Center for Proteomics and Bioinformatics, Center for Synchrotron Biosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Farquhar
authors.affiliation: Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Colton
authors.affiliation: Departments of Neurosurgery and Medicine, Stony Brook University, Stony Brook, NY, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Van Nostrand
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook NY, USA ; Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA ; Photon Sciences Directorate, Brookhaven National Laboratory, Upton, NY, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Miller
keywords: Alzheimer’s disease; X-ray absorption spectroscopy; X-ray fluorescence microscopy; amyloid plaques; copper; infrared microscopy; iron; transgenic mice