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ACS Chem Neurosci. 2017 Mar 15;8(3):629-637. doi: 10.1021/acschemneuro.6b00362. Epub 2016 Dec 22.

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.

Author information

1
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
2
Australian Synchrotron , Clayton, Victoria 3168, Australia.
3
Biomedical Manufacturing, CSIRO Manufacturing, Clayton South, Victoria 3169, Australia.
4
Elemental Bio-imaging Facility, University of Technology Sydney , Broadway, Sydney, New South Wales 2007, Australia.

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.

KEYWORDS:

Aβ plaques; XFM mapping; copper; iron; zinc

PMID:
27958708
DOI:
10.1021/acschemneuro.6b00362
[Indexed for MEDLINE]

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