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Cell Chem Biol. 2017 Oct 19;24(10):1205-1215.e3. doi: 10.1016/j.chembiol.2017.07.014. Epub 2017 Sep 7.

Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease.

Author information

1
Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK. Electronic address: n.d.telling@keele.ac.uk.
2
Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK.
3
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.
4
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.
5
Magnetic Spectroscopy Group, Diamond Light Source, Didcot, Oxfordshire OX11 ODE, UK.
6
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
7
Canadian Light Source Inc., 44 Innovation Boulevard, Saskatoon, SK S7N 2V3, Canada.
8
BIMR and Department of Chemistry, McMaster University, Hamilton, ON L8S 4M1, Canada.

Abstract

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.

KEYWORDS:

Alzheimer's disease; STXM; X-ray spectromicroscopy; amyloid-beta; diffuse plaque; ferrous iron; magnetite; redox-active iron; scanning transmission X-ray microscopy; x-ray magnetic circular dichroism

PMID:
28890316
DOI:
10.1016/j.chembiol.2017.07.014
[Indexed for MEDLINE]
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