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Nanoscale chemical speciation of β-amyloid/iron aggregates using soft X-ray spectromicroscopy

DOI: 10.1039/D0QI01304H DOI Help

Authors: James Everett (Keele University; University of Warwick) , Jake Brooks (University of Warwick) , Joanna F. Collingwood (Warwick University) , Neil Telling (Keele University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Inorganic Chemistry Frontiers , VOL 8 , PAGES 1439 - 1448

State: Published (Approved)
Published: March 2021

Open Access Open Access

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 β-amyloid (Aβ), 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 Aβ 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 Aβ 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 Aβ. Furthermore, aggregates were formed that were morphologically and chemically distinct dependent on the treatment of Aβ prior to the addition of ferric iron. These findings support the hypothesis that Aβ 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.

Subject Areas: Chemistry, Biology and Bio-materials

Facility: PolLux at Swiss Light Source

Added On: 21/04/2021 15:06


Discipline Tags:

Neurodegenerative Diseases Non-Communicable Diseases Health & Wellbeing Neurology Chemistry Inorganic Chemistry Life Sciences & Biotech

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