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Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease.
A signature characteristic of Alzheimer's disease (AD) is aggregation of amyloid-beta (Aβ) fibrils in the brain. Nevertheless, the links between Aβ and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Aβ1-42 peptide can in part be explained by metal ion binding interactions. Using advanced X-ray microscopy techniques at sub-micron resolution, we investigated relationships between iron biochemistry and AD pathology in intact cortex from an established mouse model over-producing Aβ. We found a direct correlation of amyloid plaque morphology with iron, and evidence for the formation of an iron-amyloid complex. We also show that iron biomineral deposits in the cortical tissue contain the mineral magnetite, and provide evidence that Aβ-induced chemical reduction of iron could occur in vivo. Our observations point to the specific role of iron in amyloid deposition and AD pathology, and may impact development of iron-modifying therapeutics for AD.
Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK. Electronic address: email@example.com.,
Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK.,
Warwick Engineering in Biomedicine, School of Engineering, University of Warwick, Coventry CV4 7AL, UK; Department of Materials Science and Engineering, University of Florida, Gainesville, FL 32611, USA.,
Department of Materials Science and Engineering, University of Florida, Gainesville, FL 32611, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, Institute for Cell Engineering and Regenerative Medicine (ICERM), University of Florida, Gainesville, FL 32611, USA.,
Magnetic Spectroscopy Group, Diamond Light Source, Didcot, Oxfordshire OX11 ODE, UK.,
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.,
Canadian Light Source Inc., 44 Innovation Boulevard, Saskatoon, SK S7N 2V3, Canada.
BIMR and Department of Chemistry, McMaster University, Hamilton, ON L8S 4M1, Canada.
Disease Models, Animal
Microscopy, Electron, Transmission
Pub Type(s)Journal Article