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

Everett, James; Brooks, Jake; Lermyte, Frederik; O’Connor, Peter B.; Sadler, Peter J.; Dobson, Jon; Collingwood, Joanna F.; Telling, Neil D.

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


Authors

Jake Brooks

Frederik Lermyte

Peter B. O’Connor

Peter J. Sadler

Jon Dobson

Joanna F. Collingwood



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 ß-amyloid (Aß) 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 Aß and ferritin resulted in the conversion of ferritin's inert ferric core into more reactive low-oxidation-states. Such findings strongly implicate Aß 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 Article Type Article
Acceptance Date May 28, 2020
Publication Date Jun 25, 2020
Journal Scientific Reports
Print ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 20
Article Number 10332
DOI https://doi.org/10.1038/s41598-020-67117-z
Keywords Alzheimer's disease; Dementia; Metals; Neurodegenerative diseases; Peptides
Publisher URL https://doi.org/10.1038/s41598-020-67117-z

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