Neil Telling n.d.telling@keele.ac.uk
Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease.
Telling, Neil; Everett, James; Collingwood, Joanna F.; Dobson, Jon; van der Laan, Gerrit; Gallagher, Joseph J.; Wang, Jian; Hitchcock, Adam P.
Authors
James Everett j.everett@keele.ac.uk
Joanna F. Collingwood
Jon Dobson
Gerrit van der Laan
Joseph J. Gallagher
Jian Wang
Adam P. Hitchcock
Abstract
A signature characteristic of Alzheimer's disease (AD) is aggregation of amyloid-beta (Aß) fibrils in the brain. Nevertheless, the links between Aß and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Aß1-42 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 Aß. 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 Aß-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.
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 28, 2017 |
Publication Date | Sep 7, 2017 |
Publicly Available Date | Mar 29, 2024 |
Journal | Cell Chemical Biology |
Print ISSN | 2451-9456 |
Publisher | Cell Press |
Peer Reviewed | Not Peer Reviewed |
Volume | 24 |
Issue | 10 |
Pages | 1205-1215 |
DOI | https://doi.org/10.1016/j.chembiol.2017.07.014 |
Keywords | Alzheimer's disease, amyloid-beta, redox-active iron, ferrous iron, magnetite, X-ray spectromicroscopy, scanning transmission X-ray microscopy, STXM, x-ray magnetic circular dichroism, diffuse plaque |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S2451945617302726?via%3Dihub |
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