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Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42)

DOI: 10.1038/s41598-020-67117-z DOI Help

Authors: James Everett (Keele University; University of Warwick) , Jake Brooks (University of Warwick) , Frederik Lermyte (University of Warwick) , Peter B. O’connor (University of Warwick) , Peter J. Sadler (University of Warwick) , Jon Dobson (University of Florida) , Joanna F. Collingwood (Warwick University) , Neil D. Telling (Keele University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Scientific Reports , VOL 10

State: Published (Approved)
Published: June 2020

Open Access Open Access

Abstract: Atypical low-oxidation-state iron phases in Alzheimer’s disease (AD) pathology are implicated in disease pathogenesis, as they may promote elevated redox activity and convey toxicity. However, the origin of low-oxidation-state iron and the pathways responsible for its formation and evolution remain unresolved. Here we investigate the interaction of the AD peptide β-amyloid (Aβ) with the iron storage protein ferritin, to establish whether interactions between these two species are a potential source of low-oxidation-state iron in AD. Using X-ray spectromicroscopy and electron microscopy we found that the co-aggregation of Aβ and ferritin resulted in the conversion of ferritin’s inert ferric core into more reactive low-oxidation-states. Such findings strongly implicate Aβ in the altered iron handling and increased oxidative stress observed in AD pathogenesis. These amyloid-associated iron phases have biomarker potential to assist with disease diagnosis and staging, and may act as targets for therapies designed to lower oxidative stress in AD tissue.

Journal Keywords: Alzheimer's disease; Dementia; Metals; Neurodegenerative diseases; Peptides

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I08-Scanning X-ray Microscopy beamline (SXM) , I10-Beamline for Advanced Dichroism

Other Facilities: PolLux beamline at Swiss Light Source