Nanoscale correlation of iron biochemistry with amyloid plaque morphology in Alzheimer’s disease transgenic mouse cortex

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., …Hitchcock, A. P. (2017). Nanoscale correlation of iron biochemistry with amyloid plaque morphology in Alzheimer’s disease transgenic mouse cortex. 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
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 10
• Pages: 1205-1215
• DOI: https://doi.org/10.1016/j.chembiol.2017.07.014
• Keywords: Alzheimer's diseaseamyloid-betaredox-active ironferrous ironmagnetiteX-ray spectromicroscopyscanning transmission X-ray microscopySTXMx-ray magnetic circular dichroismdiffuse plaque
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2451945617302726?via%3Dihub