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

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 re...

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Bibliographic Details
Published in:Scientific reports 2020-06, Vol.10 (1), p.10332-10332, Article 10332
Main Authors: Everett, James, Brooks, Jake, Lermyte, Frederik, O'Connor, Peter B, Sadler, Peter J, Dobson, Jon, Collingwood, Joanna F, Telling, Neil D
Format: Article
Language:English
Subjects:
Alzheimer Disease - diagnosis
Alzheimer Disease - pathology
Alzheimer's disease
Amyloid beta-Peptides - metabolism
Amyloid beta-Peptides - ultrastructure
Biomarkers - chemistry
Biomarkers - metabolism
Electron microscopy
Ferritin
Ferritins - chemistry
Ferritins - metabolism
Ferritins - ultrastructure
Humans
Iron
Iron - chemistry
Iron - metabolism
Microscopy, Electron, Scanning Transmission
Neurodegenerative diseases
Oxidation
Oxidation-Reduction
Oxidative Stress
Pathogenesis
Peptide Fragments - metabolism
Peptide Fragments - ultrastructure
Protein Aggregates
Spectrometry, X-Ray Emission
Toxicity
β-Amyloid
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-67117-z