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Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide β-amyloid (1-42)
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Everett, James, Céspedes, Eva, Shelford, Leigh R., Exley, Chris, Collingwood, Joanna F., Dobson, Jon, van der Laan, Gerrit, Jenkins, Catherine A., Arenholz, Elke and Telling, Neil D. (2014) Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide β-amyloid (1-42). Journal of The Royal Society Interface, Volume 11 (Number 95). Article number 20140165. doi:10.1098/rsif.2014.0165
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Official URL: http://dx.doi.org/10.1098/rsif.2014.0165
Abstract
For decades, a link between increased levels of iron and areas of Alzheimer's disease (AD) pathology has been recognized, including AD lesions comprised of the peptide β-amyloid (Aβ). Despite many observations of this association, the relationship between Aβ and iron is poorly understood. Using X-ray microspectroscopy, X-ray absorption spectroscopy, electron microscopy and spectrophotometric iron(II) quantification techniques, we examine the interaction between Aβ(1–42) and synthetic iron(III), reminiscent of ferric iron stores in the brain. We report Aβ to be capable of accumulating iron(III) within amyloid aggregates, with this process resulting in Aβ-mediated reduction of iron(III) to a redox-active iron(II) phase. Additionally, we show that the presence of aluminium increases the reductive capacity of Aβ, enabling the redox cycling of the iron. These results demonstrate the ability of Aβ to accumulate iron, offering an explanation for previously observed local increases in iron concentration associated with AD lesions. Furthermore, the ability of iron to form redox-active iron phases from ferric precursors provides an origin both for the redox-active iron previously witnessed in AD tissue, and the increased levels of oxidative stress characteristic of AD. These interactions between Aβ and iron deliver valuable insights into the process of AD progression, which may ultimately provide targets for disease therapies.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QP Physiology | ||||||
| Divisions: | Faculty of Science > Engineering | ||||||
| Library of Congress Subject Headings (LCSH): | Iron in the body, Amyloid beta-protein | ||||||
| Journal or Publication Title: | Journal of The Royal Society Interface | ||||||
| Publisher: | The Royal Society Publishing | ||||||
| ISSN: | 1742-5689 | ||||||
| Official Date: | June 2014 | ||||||
| Dates: |
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| Date of first compliant deposit: | 24 June 2016 | ||||||
| Volume: | Volume 11 | ||||||
| Number: | Number 95 | ||||||
| Article Number: | Article number 20140165 | ||||||
| DOI: | 10.1098/rsif.2014.0165 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access | ||||||
| Funder: | Diamond Light Source (Firm), United States. Department of Energy, Engineering and Physical Sciences Research Council (EPSRC) | ||||||
| Grant number: | DE-AC02-05CH11231 (DoE), EP/P503981 (EPSRC) |
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