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Nanoscale chemical speciation of ß-amyloid/iron aggregates using soft x-ray spectromicroscopy

Everett, James; Brooks, Jake; Collingwood, Joanna F.; Telling, Neil

Nanoscale chemical speciation of ß-amyloid/iron aggregates using soft x-ray spectromicroscopy Thumbnail


Authors

Jake Brooks

Joanna F. Collingwood



Abstract

Iron (Fe) is an essential trace element required for healthy brain function. Yet, disrupted iron neurochemistry, and the associated formation of aberrantly aggregated protein lesions has been implicated in the development of multiple degenerative brain disorders including Alzheimer's disease (AD). Here, nanoscale resolution soft X-ray spectromicroscopy is used to examine the interaction of ß-amyloid (Aß), a peptide fundamentally implicated in the development of Alzheimer's, and ferric (Fe3+) iron. Crucially, by probing the carbon K (280–320 eV) and iron L2,3 (700–740 eV) edges, both the organic and inorganic (iron) sample chemistry was established. The co-aggregation of Aß and iron is known to influence iron chemistry, resulting in the chemical reduction of Fe3+ into reactive and potentially toxic ferrous (Fe2+) and zero-oxidation (Fe0) states. Here, nanoscale (i.e. sub-micron) variations in both iron oxidation state and the organic composition of Aß were observed, replicating in vitro the diverse iron chemistry documented in amyloid plaques from human brain, with the chemical state of iron linked to the conformation state of Aß. Furthermore, aggregates were formed that were morphologically and chemically distinct dependent on the treatment of Aß prior to the addition of ferric iron. These findings support the hypothesis that Aß is responsible for altering iron neurochemistry, and that this altered chemistry is a factor in neurodegenerative processes documented in AD. The methods applied here, combining nanoscale-resolution imaging and high chemical sensitivity, enabled discovery of the nanoscale heterogeneity in the iron and carbon chemistry of in vitro aggregates, and these approaches have scope for wider application in metallomics.

Journal Article Type Article
Acceptance Date Jan 6, 2021
Publication Date Jan 15, 2021
Publicly Available Date Mar 29, 2024
Journal Inorganic Chemistry Frontiers
Print ISSN 2052-1553
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 8
Issue 6
Pages 1439-1448
DOI https://doi.org/10.1039/D0QI01304H
Publisher URL https://pubs.rsc.org/en/content/articlelanding/2021/QI/D0QI01304H#!divAbstract

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