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dc.contributor.authorEverett, J.
dc.contributor.authorCespedes, E.
dc.contributor.authorShelford, L.R.
dc.contributor.authorExley, C.
dc.contributor.authorCollingwood, J.F.
dc.contributor.authorDobson, J.
dc.contributor.authorvan der Laan, Gerrit
dc.contributor.authorJenkins, C.A.
dc.contributor.authorArenholz, E.
dc.contributor.authorTelling, N.D.
dc.date.accessioned2014-10-24T14:33:47Z
dc.date.issued2014
dc.description.abstractFor 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.en_GB
dc.description.sponsorshipDiamond Light Source Ltd.en_GB
dc.description.sponsorshipEPSRC (Engineering and Physical Sciences Research Council)en_GB
dc.identifier.citationVol. 11 (95), article 20140165en_GB
dc.identifier.doi10.1098/rsif.2014.0165
dc.identifier.grantnumberDoctoral studentshipen_GB
dc.identifier.grantnumberEP/P503981en_GB
dc.identifier.urihttp://hdl.handle.net/10871/15734
dc.language.isoenen_GB
dc.publisherRoyal Scocietyen_GB
dc.relation.urlhttp://dx.doi.org/10.1098/rsif.2014.0165en_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/24671940en_GB
dc.rightsPublished under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.en_GB
dc.subjectAlzheimer's diseaseen_GB
dc.subjectX-ray absorptionen_GB
dc.subjectredoxen_GB
dc.subjectwüstiteen_GB
dc.subjectβ-amyloiden_GB
dc.titleFerrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide β-amyloid (1-42).en_GB
dc.typeArticleen_GB
dc.date.available2014-10-24T14:33:47Z
exeter.place-of-publicationEngland
dc.descriptionCopyright © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.en_GB
dc.descriptionOpen Access articleen_GB
dc.descriptionPubMed ID: 24671940en_GB
dc.identifier.eissn1742-5662
dc.identifier.journalJournal of the Royal Society Interfaceen_GB


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