Telling, ND and Everett, J and Collingwood, JF and Dobson, J and van der Laan, G and Gallagher, JJ and Wang, J and Hitchcock, AP (2017) Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease. Cell Chemical Biology. ISSN 2451-9456

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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.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Elsevier at http://dx.doi.org/10.1016/j.chembiol.2017.07.014 - please refer to any applicable terms of use of the publisher.
Uncontrolled 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
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC346 Neurology. Diseases of the nervous system, including speech disorders
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Related URLs:
Depositing User: Symplectic
Date Deposited: 05 Oct 2017 10:44
Last Modified: 10 Oct 2017 13:33
URI: http://eprints.keele.ac.uk/id/eprint/4074

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