Affiliations: [a] Department of Physiology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland | [b] School of Engineering, University of Warwick, Coventry, UK | [c] Institute of Science and Technology in Medicine, Keele University, Stoke-on-Trent, UK | [d] Departments of Biomedical Engineering and Materials Science and Engineering, University of Florida, Gainesville, Florida, USA
Correspondence:
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Correspondence to: Joseph J. Gallagher, Biological Imaging Centre, Beckman Institute, m/c 139-74, California Institute of Technology, Pasadena, California, USA. Tel.: +1 626 395 2004; Fax: +1 626 449 5163; E-mail: jjg@caltech.edu.
Abstract: There is a well-established literature indicating a relationship between iron in brain tissue and Alzheimer's disease (AD). More recently, it has become clear that AD is associated with neuroinflammatory and oxidative changes which probably result from microglial activation. In this study, we investigated the correlative changes in microglial activation, oxidative stress, and iron dysregulation in a mouse model of AD which exhibits early-stage amyloid deposition. Microfocus X-ray absorption spectroscopy analysis of intact brain tissue sections prepared from AβPP/PS1 transgenic mice revealed the presence of magnetite, a mixed-valence iron oxide, and local elevations in iron levels in tissue associated with amyloid-β-containing plaques. The evidence indicates that the expression of markers of microglial activation, CD11b and CD68, and astrocytic activation, GFAP, were increased, and were histochemically determined to be adjacent to amyloid-β-containing plaques. These findings support the contention that, in addition to glial activation and oxidative stress, iron dysregulation is an early event in AD pathology.
