title: Evidence of redox-active iron formation following aggregation of ferrihydrite and the Alzheimer's disease peptide β-amyloid.
abstract: Recent work has demonstrated increased levels of redox-active iron biominerals in Alzheimer's disease (AD) tissue. However, the origin, nature, and role of iron in AD pathology remains unclear. Using X-ray absorption, X-ray microspectroscopy, and electron microscopy techniques, we examined interactions between the AD peptide β-amyloid (Aβ) and ferrihydrite, which is the ferric form taken when iron is stored in humans. We report that Aβ is capable of reducing ferrihydrite to a pure iron(II) mineral where antiferromagnetically ordered Fe(2+) cations occupy two nonequivalent crystal symmetry sites. Examination of these iron(II) phases following air exposure revealed a material consistent with the iron(II)-rich mineral magnetite. These results demonstrate the capability of Aβ to induce the redox-active biominerals reported in AD tissue from natural iron precursors. Such interactions between Aβ and ferrihydrite shed light upon the processes of AD pathogenesis, while providing potential targets for future therapies.
authors.affiliation: Institute for Science and Technology in Medicine, Keele University , Stoke-on-Trent, Staffordshire ST4 7QB, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Everett
authors.forename: Eva
authors.initials: E
authors.lastname: Céspedes
authors.forename: Leigh R
authors.initials: LR
authors.lastname: Shelford
authors.forename: Chris
authors.initials: C
authors.lastname: Exley
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Collingwood
authors.forename: Jon
authors.initials: J
authors.lastname: Dobson
authors.forename: Gerrit
authors.initials: G
authors.lastname: van der Laan
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Jenkins
authors.forename: Elke
authors.initials: E
authors.lastname: Arenholz
authors.forename: Neil D
authors.initials: ND
authors.lastname: Telling
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000737:chemistry*; D017348:Microscopy, Electron, Scanning Transmission; D010084:Oxidation-Reduction
chemical_list: D016229:Amyloid beta-Peptides; D005290:Ferric Compounds; C092844:ferric oxyhydroxide; D007501:Iron