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Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease.
Cell Chem Biol 2017; 24(10):1205-1215.e3CC

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.

Authors+Show Affiliations

Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK. Electronic address: n.d.telling@keele.ac.uk.Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK.Warwick Engineering in Biomedicine, School of Engineering, University of Warwick, Coventry CV4 7AL, UK; Department of Materials Science and Engineering, University of Florida, Gainesville, FL 32611, USA.Department of Materials Science and Engineering, University of Florida, Gainesville, FL 32611, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, Institute for Cell Engineering and Regenerative Medicine (ICERM), University of Florida, Gainesville, FL 32611, USA.Magnetic Spectroscopy Group, Diamond Light Source, Didcot, Oxfordshire OX11 ODE, UK.Department of Physiology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.Canadian Light Source Inc., 44 Innovation Boulevard, Saskatoon, SK S7N 2V3, Canada.BIMR and Department of Chemistry, McMaster University, Hamilton, ON L8S 4M1, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28890316

Citation

Telling, Neil D., et al. "Iron Biochemistry Is Correlated With Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease." Cell Chemical Biology, vol. 24, no. 10, 2017, pp. 1205-1215.e3.
Telling ND, Everett J, Collingwood JF, et al. Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease. Cell Chem Biol. 2017;24(10):1205-1215.e3.
Telling, N. D., Everett, J., Collingwood, J. F., Dobson, J., van der Laan, G., Gallagher, J. J., ... Hitchcock, A. P. (2017). Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease. Cell Chemical Biology, 24(10), pp. 1205-1215.e3. doi:10.1016/j.chembiol.2017.07.014.
Telling ND, et al. Iron Biochemistry Is Correlated With Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease. Cell Chem Biol. 2017 Oct 19;24(10):1205-1215.e3. PubMed PMID: 28890316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease. AU - Telling,Neil D, AU - Everett,James, AU - Collingwood,Joanna F, AU - Dobson,Jon, AU - van der Laan,Gerrit, AU - Gallagher,Joseph J, AU - Wang,Jian, AU - Hitchcock,Adam P, Y1 - 2017/09/07/ PY - 2015/06/19/received PY - 2017/01/19/revised PY - 2017/07/28/accepted PY - 2017/9/12/pubmed PY - 2017/10/31/medline PY - 2017/9/12/entrez KW - Alzheimer's disease KW - STXM KW - X-ray spectromicroscopy KW - amyloid-beta KW - diffuse plaque KW - ferrous iron KW - magnetite KW - redox-active iron KW - scanning transmission X-ray microscopy KW - x-ray magnetic circular dichroism SP - 1205 EP - 1215.e3 JF - Cell chemical biology JO - Cell Chem Biol VL - 24 IS - 10 N2 - 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. SN - 2451-9448 UR - https://www.unboundmedicine.com/medline/citation/28890316/Iron_Biochemistry_is_Correlated_with_Amyloid_Plaque_Morphology_in_an_Established_Mouse_Model_of_Alzheimer's_Disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2451-9456(17)30272-6 DB - PRIME DP - Unbound Medicine ER -