title: Iron, Copper, and Zinc Concentration in Aβ Plaques in the APP/PS1 Mouse Model of Alzheimer's Disease Correlates with Metal Levels in the Surrounding Neuropil.
abstract: The metal ions of iron, copper, and zinc have long been associated with the aggregation of β-amyloid (Aβ) plaques in Alzheimer's disease; an interaction that has been suggested to promote increased oxidative stress and neuronal dysfunction. We examined plaque metal load in the hippocampus of APP/PS1 mice using X-ray fluorescence microscopy to assess how the anatomical location of Aβ plaques was influenced by the metal content of surrounding tissue. Immunohistochemical staining of Aβ plaques colocalized with areas of increased X-ray scattering power in unstained tissue sections, allowing direct X-ray based-assessment of plaque metal levels in sections subjected to minimal chemical fixation. We identified and mapped 48 individual plaques in four subregions of the hippocampus from four biological replicates. Iron, Cu, and Zn areal concentrations (ng cm-2) were increased in plaques compared to the surrounding neuropil. However, this elevation in metal load reflected the local metal makeup of the surrounding neuropil, where different brain regions are enriched for different metal ions. After correcting for tissue density, only Zn levels remained elevated in plaques. This study suggests that the in vivo binding of Zn to plaques is not simply due to increased protein deposition.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.|Australian Synchrotron , Clayton, Victoria 3168, Australia.
authors.forename: Simon A
authors.initials: SA
authors.lastname: James
authors.affiliation: Biomedical Manufacturing, CSIRO Manufacturing, Clayton South, Victoria 3169, Australia.
authors.forename: Quentin I
authors.initials: QI
authors.lastname: Churches
authors.affiliation: Australian Synchrotron , Clayton, Victoria 3168, Australia.
authors.forename: Martin D
authors.initials: MD
authors.lastname: de Jonge
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Ian E
authors.initials: IE
authors.lastname: Birchall
authors.affiliation: Biomedical Manufacturing, CSIRO Manufacturing, Clayton South, Victoria 3169, Australia.
authors.forename: Victor
authors.initials: V
authors.lastname: Streltsov
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Gawain
authors.initials: G
authors.lastname: McColl
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.|Elemental Bio-imaging Facility, University of Technology Sydney , Broadway, Sydney, New South Wales 2007, Australia.
authors.forename: Dominic J
authors.identifier: 0000-0002-5922-7643
authors.initials: DJ
authors.lastname: Hare
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000473:pathology*; D003300:Copper / Q000737:chemistry*; D004195:Disease Models, Animal; D006801:Humans; D007501:Iron / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D019581:Neuropil / Q000737:chemistry*; D058225:Plaque, Amyloid / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D014965:X-Rays; D015032:Zinc / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008670:Metals; C508853:PSEN1 protein, human; D053764:Presenilin-1; D003300:Copper; D007501:Iron; D015032:Zinc
keywords: Aβ plaques; XFM mapping; copper; iron; zinc