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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.

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


Authors

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Peer Reviewed Not Peer Reviewed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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