Abstract
There is an increasing body of evidence suggesting that metal homeostasis is dysregulated in the pathology of Alzheimer's disease (AD). Although expression levels of several transporters belonging the SLC30 family, which comprises predominantly zinc transporters, have been studied in the AD brain, SLC30A10 (ZnT10) has not been studied in this context. To determine if dysregulated expression of ZnT10, which may transport both Zn and Mn, could be a factor that contributes to AD, we investigated if there were differences in ZnT10 mRNA levels in specimens of frontal cortex from AD patients and controls and also if brain tissue from the APP/PS1 transgenic (Tg) mouse model showed abnormal levels of ZnT10 mRNA expression. Our results show that ZnT10 is significantly (P<0.01) decreased in the frontal cortex in AD. Furthermore, we observed a significant decrease in ZnT10 mRNA levels in the APP/PS1-Tg mice compared with wild-type controls (P<0.01). Our results suggest that this dysregulation in ZnT10 could further contribute to disease progression.
Highlights
Zn is thought to be involved in Alzheimer’s disease (AD) development and progression, there are many questions that remain unanswered
To determine if dys-regulated expression of ZnT10 could be a factor that contributes to AD, we investigated if there were differences in ZnT10 mRNA levels in specimens of frontal cortex from AD patients and controls and if brain tissue from the amyloid precursor protein (APP)/PS1 transgenic (Tg) mouse model showed abnormal levels of ZnT10 mRNA expression
To investigate if there is any association between levels of ZnT10 expression in relevant regions of the brain and AD, we measured ZnT10 mRNA in frontal cortex of AD patients and controls and in frontal cortex of 12 month old female wild-type and APP/PS1 mice
Summary
Zn is thought to be involved in Alzheimer’s disease (AD) development and progression, there are many questions that remain unanswered. Upregulation of ZnT1 protein in the hippocampus in AD brain tissue has been observed [3]. It is thought that this increase in ZnT1 expression in the disease state causes an increase in Zn ions available in the extracellular space for initiation of Ab deposition and senile plaque formation [4]. In the preclinical disease states mild cognitive impairment and pre-clinical AD- an initial decrease in ZnT1 is observed before progression to AD. Additional members of the ZnT family of Zn transporters, ZnT4 and ZnT6, have been implicated in AD progression, with elevated protein levels of both transporters in the hippocampus of AD patients [5]
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