Abstract
The ZnT3 zinc transporter is uniquely expressed in cortical glutamatergic synapses where it organizes zinc release into the synaptic cleft and mediates beta-amyloid deposition in transgenic mice. We studied the association of zinc in plaques in relation to cytoarchitectural zinc localization in the APP/PS1 transgenic mouse model of Alzheimer's disease. The effects of low dietary zinc for 3 months upon brain pathology were also studied. We determined that synaptic zinc distribution within cortical layers is paralleled by amyloid burden, which is heaviest for both in layers 2-3 and 5. ZnT3 immunoreactivity is prominent in dystrophic neurites within amyloid plaques. Low dietary zinc caused a significant 25% increase in total plaque volume in Alzheimer's mice using stereological measures. The level of oxidized proteins in brain tissue did not changed in animals on a zinc-deficient diet compared with controls. No obvious changes were observed in the autometallographic pattern of zinc-enriched terminals in the neocortex or in the expression levels of zinc transporters, zinc importers or metallothioneins. A small decrease in plasma zinc induced by the low-zinc diet was consistent with the subclinical zinc deficiency that is common in older human populations. While the mechanism remains uncertain, our findings indicate that subclinical zinc deficiency may be a risk factor for Alzheimer's pathology.
Original language | English |
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Journal | Neuroscience |
Volume | 150 |
Issue number | 2 |
Pages (from-to) | 357-69 |
Number of pages | 13 |
ISSN | 0306-4522 |
DOIs | |
Publication status | Published - 5 Dec 2007 |
Externally published | Yes |
Keywords
- Alzheimer Disease/genetics
- Amyloid beta-Peptides/biosynthesis
- Amyloid beta-Protein Precursor/genetics
- Animals
- Cerebral Cortex/metabolism
- Female
- Food, Formulated
- Male
- Mice
- Mice, Transgenic
- Nutritional Requirements
- Plaque, Amyloid/metabolism
- Presenilin-1/genetics
- Risk Factors
- Zinc/deficiency