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.

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.

Citation

Telling, N., Everett, J., Collingwood, J. F., Dobson, J., van der Laan, G., Gallagher, J. J., Wang, J., & Hitchcock, A. P. (2017). Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease. Cell chemical biology, 24(10), 1205-1215. https://doi.org/10.1016/j.chembiol.2017.07.014

• Journal Article Type: Article
• Acceptance Date: Jul 28, 2017
• Publication Date: Sep 7, 2017
• Journal: Cell Chemical Biology
• Print ISSN: 2451-9456
• Electronic ISSN: 2451-9448
• 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• Peer Reviewed: Not Peer Reviewed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
• Public URL: https://keele-repository.worktribe.com/output/409502
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S2451945617302726?via%3Dihub