Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease. Issue 10 (19th October 2017)

• Record Type: Journal Article
• Authors: Telling, Neil D.; Everett, James; Collingwood, Joanna F.; Dobson, Jon; van der Laan, Gerrit; Gallagher, Joseph J.; Wang, Jian; Hitchcock, Adam P.
• Is Part Of: Cell chemical biology. Volume 24:Issue 10(2017)
• Page Start: 1205
• Page End: 1215.e3
• Publication Date: 2017-10-19
• Subjects: 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; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2017.07.014
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: 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. Graphical Abstract: Highlights: Chemically reduced pure ferrous iron is directly associated with amyloid pathology Diffuse amyloid deposits could comprise an iron-amyloid complex Magnetic signature of particulate magnetite detected with varying oxidation state Abstract : Telling et al. demonstrate an enhanced role for iron in Alzheimer's disease pathology, having implications for neurodegeneration, early-stage diagnosis by MRI, and possible treatments based on metal chelation.