Article type: Research Article
Authors: Bourassa, Megan W. | Leskovjan, Andreana C. | Tappero, Ryan V. | Farquhar, Erik R. | Colton, Carol A. | Van Nostrand, William E. | Miller, Lisa M.; ; ;
Affiliations: 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 | Center for Proteomics and Bioinformatics, Center for Synchrotron Biosciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA | Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC, USA | Departments of Neurosurgery and Medicine, Stony Brook University, Stony Brook, NY, USA
Note:  Corresponding author: Lisa M. Miller, PhD, Photon Sciences Directorate, Bldg. 725D, Brookhaven National Laboratory, 75 Brookhaven Avenue, Upton, NY 11973-5000, USA. Tel.: +1 631 344 2091; Fax: +1 631 344 3238; E-mail: [email protected]
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.
Keywords: Alzheimer's disease, amyloid plaques, copper, iron, transgenic mice, X-ray fluorescence microscopy, X-ray absorption spectroscopy, infrared microscopy
Journal: Biomedical Spectroscopy and Imaging, vol. 2, no. 2, pp. 129-139, 2013