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Iron biochemistry is correlated with amyloid plaque morphology in an established mouse model of Alzheimer’s disease
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Telling, Neil D., Everett, James, Collingwood, Joanna F., Dobson, Jon, van der Laan, Gerrit, Gallagher, Joseph J., Wang, Jian and Hitchcock, Adam P. (2017) Iron biochemistry is correlated with amyloid plaque morphology in an established mouse model of Alzheimer’s disease. Cell Chemical Biology, 24 (10). 1205-1215.E3. doi:10.1016/j.chembiol.2017.07.014
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Official URL: http://dx.doi.org/10.1016/j.chembiol.2017.07.014
Abstract
A signature characteristic of Alzheimer's disease (AD) is aggregation of amyloid-beta (Aβ) fibrils in the brain. Nevertheless, the links between Aβ and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Aβ1-42 peptide can in part be explained by metal ion binding interactions. Using advanced X-ray microscopy techniques at sub-micron resolution, we investigated relationships between iron biochemistry and AD pathology in intact cortex from an established mouse model over-producing Aβ. We found a direct correlation of amyloid plaque morphology with iron, and evidence for the formation of an iron-amyloid complex. We also show that iron biomineral deposits in the cortical tissue contain the mineral magnetite, and provide evidence that Aβ-induced chemical reduction of iron could occur in vivo. Our observations point to the specific role of iron in amyloid deposition and AD pathology, and may impact development of iron-modifying therapeutics for AD.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QP Physiology | ||||||||
| Divisions: | Faculty of Science > Engineering | ||||||||
| Library of Congress Subject Headings (LCSH): | Alzheimer's disease -- Molecular aspects, Amyloid beta-protein, Neurotoxicology, X-ray microscopy, Iron in the body, Iron -- Physiological effect | ||||||||
| Journal or Publication Title: | Cell Chemical Biology | ||||||||
| Publisher: | Cell Press | ||||||||
| ISSN: | 2451-9456 | ||||||||
| Official Date: | October 2017 | ||||||||
| Dates: |
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| Date of first compliant deposit: | 18 September 2017 | ||||||||
| Volume: | 24 | ||||||||
| Number: | 10 | ||||||||
| Page Range: | 1205-1215.E3 | ||||||||
| DOI: | 10.1016/j.chembiol.2017.07.014 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Funder: | Engineering and Physical Sciences Research Council (EPSRC) | ||||||||
| Grant number: | EP/D066654/1, EP/K035193/1 |
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