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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2009

Open Access 01-12-2009 | Research article

ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain

Authors: Nancy Beyer, David TR Coulson, Shirley Heggarty, Rivka Ravid, G Brent Irvine, Jan Hellemans, Janet A Johnston

Published in: Molecular Neurodegeneration | Issue 1/2009

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Abstract

Background

ZnT3 is a membrane Zn2+ transporter that is responsible for concentrating Zn2+ into neuronal presynaptic vesicles. Zn2+ homeostasis in the brain is relevant to Alzheimer's disease (AD) because Zn2+ released during neurotransmission may bind to Aβ peptides, accelerating the assembly of Aβ into oligomers which have been shown to impair synaptic function.

Results

We quantified ZnT3 mRNA levels in Braak-staged human post mortem (pm) brain tissue from medial temporal gyrus, superior occipital gyrus, superior parietal gyrus, superior frontal gyrus and cerebellum from individuals with AD (n = 28), and matched controls (n = 5) using quantitative real-time PCR. ZnT3 mRNA levels were significantly decreased in all four cortical regions examined in the AD patients, to 45-60% of control levels. This reduction was already apparent at Braak stage 4 in most cortical regions examined. Quantification of neuronal and glial-specific markers in the same samples (neuron-specific enolase, NSE; and glial fibrillary acidic protein, GFAP) indicated that loss of cortical ZnT3 expression was more pronounced, and occurred prior to, significant loss of NSE expression in the tissue. Significant increases in cortical GFAP expression were apparent as the disease progressed. No gene expression changes were observed in the cerebellum, which is relatively spared of AD neuropathology.

Conclusions

This first study to quantify ZnT3 mRNA levels in human pm brain tissue from individuals with AD and controls has revealed a significant loss of ZnT3 expression in cortical regions, suggesting that neuronal cells in particular show reduced expression of ZnT3 mRNA in the disease. This suggests that altered neuronal Zn2+ handling may be an early event in AD pathogenesis.
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Metadata
Title
ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain
Authors
Nancy Beyer
David TR Coulson
Shirley Heggarty
Rivka Ravid
G Brent Irvine
Jan Hellemans
Janet A Johnston
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2009
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-4-53

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