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

DOI: 10.1016/j.chembiol.2017.07.014 DOI Help

Authors: Neil D. Telling (Keele University) , James Everett (Keele University) , Joanna F. Collingwood (University of Warwick; University of Florida) , Jon Dobson (Keele University; University of Florida) , Gerrit Van Der Laan (Diamond Light Source) , Joseph J. Gallagher (Trinity College Dublin) , Jian Wang (Canadian Light Source Inc) , Adam P. Hitchcock (McMaster University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Chemical Biology

State: Published (Approved)
Published: September 2017

Abstract: A signature characteristic of Alzheimer’s disease (AD) is aggregation of amyloid-beta (Ab) fibrils in the brain. Nevertheless, the links between Ab and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Ab1-42 peptide can in part be explained by metal ion binding interactions. Using advanced X-ray microscopy techniques at submicron resolution, we investigated relationships between iron biochemistry and AD pathology in intact cortex from an established mouse model over-producing Ab. 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 Ab-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 Keywords: Alzheimer’s disease, STXM

Subject Areas: Medicine, Biology and Bio-materials, Chemistry

Facility: Canadian Light Source