Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide ß-amyloid (1-42).

Everett; Telling

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 ß-amyloid (Aß). Despite many observations of this association, the relationship between Aß 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 Aß(1-42) and synthetic iron(III), reminiscent of ferric iron stores in the brain. We report Aß to be capable of accumulating iron(III) within amyloid aggregates, with this process resulting in Aß-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 Aß, enabling the redox cycling of the iron. These results demonstrate the ability of Aß 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 Aß and iron deliver valuable insights into the process of AD progression, which may ultimately provide targets for disease therapies.

Citation

Everett, & Telling. (2014). Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide ß-amyloid (1-42). Journal of the Royal Society. Interface, 20140165 - ?. https://doi.org/10.1098/rsif.2014.0165

• Acceptance Date: Mar 3, 2014
• Publication Date: Jun 6, 2014
• Journal: Journal of the Royal Society Interface
• Print ISSN: 1742-5689
• Electronic ISSN: 1742-5662
• Publisher: The Royal Society
• Peer Reviewed: Peer Reviewed
• Pages: 20140165 - ?
• DOI: https://doi.org/10.1098/rsif.2014.0165
• Keywords: wustite; redox; Alzheimer's disease; X-ray absorption
• Public URL: https://keele-repository.worktribe.com/output/417318
• Publisher URL: https://royalsocietypublishing.org/doi/10.1098/rsif.2014.0165