Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease

Mark A. Lovell; Jennifer L. Smith; Shuling Xiong; William R. Markesbery

doi:10.1007/BF03033884

Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease

Mark A. Lovell, Jennifer L. Smith, Shuling Xiong, William R. Markesbery

Research output: Contribution to journal › Article › peer-review

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Abstract

Several studies show increased levels of zinc (Zn) in the Alzheimer's disease (AD) brain. More recently, alterations in synaptic Zn and Zn transporter proteins (ZnT) have been implicated in the accumulation of amyloid plaques in an animal model of AD. To determine if alterations in ZnT proteins are present in AD brain, we measured levels of ZnT-1, the protein responsible for export of Zn to the extracellular space in the amygdala (AMY), hip-pocampus/parahippocampal gyrus (HPG), superior and middle temporal gyrus (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of 19 AD and 14 age-matched control subjects. To determine if alterations of ZnT-1 occur early in the progression of AD, we analyzed protein levels in the HPG, SMTG and CER of 5 subjects with mild cognitive impairment (MCI), 5 subjects with early AD (EAD) and 4 appropriately age-matched controls. Western blot and dot-blot analysis showed statistically significant (p <0.05) elevations of ZnT-1 in AD AMY, HPG, and IPL and significantly depleted ZnT-1 in AD SMTG compared to age-matched control subjects. We also observed statistically significant elevations of ZnT-1 in the HPG of EAD subjects compared with controls. In contrast to late-stage AD subjects, ZnT-1 levels were significantly decreased in HPG of subjects with MCI and were significantly elevated in the SMTG of both MCI and EAD subjects compared with age-matched controls. Correlation analysis of ZnT-1 levels and senile plaque (SP) and neurofibrillary tangle (NFT) counts in the AMY and CA1 and subiculum of AD HPG showed a significant (p < 0.05) positive correlation with SP counts and a trend towards a significant (p = 0.12) positive correlation with NFT counts in AMY. Overall, our results show alterations in one of the key proteins responsible for maintenance of Zn homeostasis early in the progression of AD suggesting that alterations in Zn balance could be involved in the pathogenesis of neuron degeneration and amyloid deposition in AD.

Original language	English
Pages (from-to)	265-271
Number of pages	7
Journal	Neurotoxicity Research
Volume	7
Issue number	4
DOIs	https://doi.org/10.1007/BF03033884
State	Published - 2005

Bibliographical note

Funding Information:
The authors thank Paula Thomason for editorial assistance, Dr. H. Liu for senile plaque and neurofibrillary tangle counts and Sonya Anderson for subject demographic data. This work was supported by National Institutes of Health grants R01-AG16269, 5P50-AG05144 and 5P01-AG05119 and by a grant from the Abercrombie Foundation.

Keywords

Alzheimer's disease
Neurofibrillary tangles
Senile plaques
Zinc transporter protein-1

ASJC Scopus subject areas

General Neuroscience
Toxicology

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10.1007/BF03033884

Cite this

@article{e799101ef998451cb0873bd9dfe45c52,

title = "Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease",

abstract = "Several studies show increased levels of zinc (Zn) in the Alzheimer's disease (AD) brain. More recently, alterations in synaptic Zn and Zn transporter proteins (ZnT) have been implicated in the accumulation of amyloid plaques in an animal model of AD. To determine if alterations in ZnT proteins are present in AD brain, we measured levels of ZnT-1, the protein responsible for export of Zn to the extracellular space in the amygdala (AMY), hip-pocampus/parahippocampal gyrus (HPG), superior and middle temporal gyrus (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of 19 AD and 14 age-matched control subjects. To determine if alterations of ZnT-1 occur early in the progression of AD, we analyzed protein levels in the HPG, SMTG and CER of 5 subjects with mild cognitive impairment (MCI), 5 subjects with early AD (EAD) and 4 appropriately age-matched controls. Western blot and dot-blot analysis showed statistically significant (p <0.05) elevations of ZnT-1 in AD AMY, HPG, and IPL and significantly depleted ZnT-1 in AD SMTG compared to age-matched control subjects. We also observed statistically significant elevations of ZnT-1 in the HPG of EAD subjects compared with controls. In contrast to late-stage AD subjects, ZnT-1 levels were significantly decreased in HPG of subjects with MCI and were significantly elevated in the SMTG of both MCI and EAD subjects compared with age-matched controls. Correlation analysis of ZnT-1 levels and senile plaque (SP) and neurofibrillary tangle (NFT) counts in the AMY and CA1 and subiculum of AD HPG showed a significant (p < 0.05) positive correlation with SP counts and a trend towards a significant (p = 0.12) positive correlation with NFT counts in AMY. Overall, our results show alterations in one of the key proteins responsible for maintenance of Zn homeostasis early in the progression of AD suggesting that alterations in Zn balance could be involved in the pathogenesis of neuron degeneration and amyloid deposition in AD.",

keywords = "Alzheimer's disease, Neurofibrillary tangles, Senile plaques, Zinc transporter protein-1",

author = "Lovell, {Mark A.} and Smith, {Jennifer L.} and Shuling Xiong and Markesbery, {William R.}",

note = "Funding Information: The authors thank Paula Thomason for editorial assistance, Dr. H. Liu for senile plaque and neurofibrillary tangle counts and Sonya Anderson for subject demographic data. This work was supported by National Institutes of Health grants R01-AG16269, 5P50-AG05144 and 5P01-AG05119 and by a grant from the Abercrombie Foundation.",

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doi = "10.1007/BF03033884",

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AU - Lovell, Mark A.

AU - Smith, Jennifer L.

AU - Xiong, Shuling

AU - Markesbery, William R.

N1 - Funding Information: The authors thank Paula Thomason for editorial assistance, Dr. H. Liu for senile plaque and neurofibrillary tangle counts and Sonya Anderson for subject demographic data. This work was supported by National Institutes of Health grants R01-AG16269, 5P50-AG05144 and 5P01-AG05119 and by a grant from the Abercrombie Foundation.

PY - 2005

Y1 - 2005

N2 - Several studies show increased levels of zinc (Zn) in the Alzheimer's disease (AD) brain. More recently, alterations in synaptic Zn and Zn transporter proteins (ZnT) have been implicated in the accumulation of amyloid plaques in an animal model of AD. To determine if alterations in ZnT proteins are present in AD brain, we measured levels of ZnT-1, the protein responsible for export of Zn to the extracellular space in the amygdala (AMY), hip-pocampus/parahippocampal gyrus (HPG), superior and middle temporal gyrus (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of 19 AD and 14 age-matched control subjects. To determine if alterations of ZnT-1 occur early in the progression of AD, we analyzed protein levels in the HPG, SMTG and CER of 5 subjects with mild cognitive impairment (MCI), 5 subjects with early AD (EAD) and 4 appropriately age-matched controls. Western blot and dot-blot analysis showed statistically significant (p <0.05) elevations of ZnT-1 in AD AMY, HPG, and IPL and significantly depleted ZnT-1 in AD SMTG compared to age-matched control subjects. We also observed statistically significant elevations of ZnT-1 in the HPG of EAD subjects compared with controls. In contrast to late-stage AD subjects, ZnT-1 levels were significantly decreased in HPG of subjects with MCI and were significantly elevated in the SMTG of both MCI and EAD subjects compared with age-matched controls. Correlation analysis of ZnT-1 levels and senile plaque (SP) and neurofibrillary tangle (NFT) counts in the AMY and CA1 and subiculum of AD HPG showed a significant (p < 0.05) positive correlation with SP counts and a trend towards a significant (p = 0.12) positive correlation with NFT counts in AMY. Overall, our results show alterations in one of the key proteins responsible for maintenance of Zn homeostasis early in the progression of AD suggesting that alterations in Zn balance could be involved in the pathogenesis of neuron degeneration and amyloid deposition in AD.

AB - Several studies show increased levels of zinc (Zn) in the Alzheimer's disease (AD) brain. More recently, alterations in synaptic Zn and Zn transporter proteins (ZnT) have been implicated in the accumulation of amyloid plaques in an animal model of AD. To determine if alterations in ZnT proteins are present in AD brain, we measured levels of ZnT-1, the protein responsible for export of Zn to the extracellular space in the amygdala (AMY), hip-pocampus/parahippocampal gyrus (HPG), superior and middle temporal gyrus (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of 19 AD and 14 age-matched control subjects. To determine if alterations of ZnT-1 occur early in the progression of AD, we analyzed protein levels in the HPG, SMTG and CER of 5 subjects with mild cognitive impairment (MCI), 5 subjects with early AD (EAD) and 4 appropriately age-matched controls. Western blot and dot-blot analysis showed statistically significant (p <0.05) elevations of ZnT-1 in AD AMY, HPG, and IPL and significantly depleted ZnT-1 in AD SMTG compared to age-matched control subjects. We also observed statistically significant elevations of ZnT-1 in the HPG of EAD subjects compared with controls. In contrast to late-stage AD subjects, ZnT-1 levels were significantly decreased in HPG of subjects with MCI and were significantly elevated in the SMTG of both MCI and EAD subjects compared with age-matched controls. Correlation analysis of ZnT-1 levels and senile plaque (SP) and neurofibrillary tangle (NFT) counts in the AMY and CA1 and subiculum of AD HPG showed a significant (p < 0.05) positive correlation with SP counts and a trend towards a significant (p = 0.12) positive correlation with NFT counts in AMY. Overall, our results show alterations in one of the key proteins responsible for maintenance of Zn homeostasis early in the progression of AD suggesting that alterations in Zn balance could be involved in the pathogenesis of neuron degeneration and amyloid deposition in AD.

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KW - Neurofibrillary tangles

KW - Senile plaques

KW - Zinc transporter protein-1

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Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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