Neurotoxicity Research

, Volume 7, Issue 4, pp 265–271

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
Article

DOI: 10.1007/BF03033884

Cite this article as:
Lovell, M.A., Smith, J.L., Xiong, S. et al. neurotox res (2005) 7: 265. doi:10.1007/BF03033884

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 Zinc transporter protein-1 Senile plaques Neurofibrillary tangles 

Copyright information

© Springer 2005

Authors and Affiliations

  • Mark A. Lovell
    • 1
    • 2
  • Jennifer L. Smith
    • 1
    • 2
  • Shuling Xiong
    • 1
  • William R. Markesbery
    • 1
    • 3
  1. 1.Sanders-Brown Center on AgingUniversity of KentuckyLexingtonUSA
  2. 2.Department of ChemistryUniversity of KentuckyLexingtonUSA
  3. 3.Departments of Neurology and PathologyUniversity of KentuckyLexingtonUSA

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