1. Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42)
- Author
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Peter J. Sadler, Jon Dobson, Jake Brooks, Peter B. O’Connor, Frederik Lermyte, Neil D. Telling, Joanna F. Collingwood, and James Everett
- Subjects
0301 basic medicine ,Microscopy, Electron, Scanning Transmission ,Iron ,lcsh:Medicine ,Peptide ,medicine.disease_cause ,Q1 ,Article ,Pathogenesis ,03 medical and health sciences ,Protein Aggregates ,0302 clinical medicine ,Alzheimer Disease ,medicine ,Humans ,Potential source ,lcsh:Science ,chemistry.chemical_classification ,Multidisciplinary ,Amyloid beta-Peptides ,biology ,Neurodegenerative diseases ,lcsh:R ,Spectrometry, X-Ray Emission ,Alzheimer's disease ,R1 ,Peptide Fragments ,Ferritin ,Oxidative Stress ,030104 developmental biology ,Biochemistry ,chemistry ,Metals ,Toxicity ,Ferritins ,biology.protein ,Ferric ,Biomarker (medicine) ,Dementia ,lcsh:Q ,Peptides ,Oxidation-Reduction ,030217 neurology & neurosurgery ,Oxidative stress ,Biomarkers ,medicine.drug - 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.
- Published
- 2020