Analysis of HSPA8 and HSPA9 mRNA expression and promoter methylation in the brain and blood of Alzheimer's disease patients

J Alzheimers Dis. 2014;38(1):165-70. doi: 10.3233/JAD-130428.

Abstract

Alzheimer's disease (AD) is the most common form of dementia in elderly. Chaperones may have a crucial role in AD due to their involvement in protein quality control, folding, and degradation. In this study, we investigated the mRNA and promoter DNA methylation levels of two chaperones, HSPA8 and HSPA9, in postmortem brain tissue (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood of healthy elderly and AD patients. mRNA quantification was performed by qRT-PCR and DNA methylation by mass spectrometry. In the peripheral blood, we did not observe a significant difference in HSPA8 and HSPA9 expression between elderly controls and AD. A significant downregulation of HSPA8 and HSPA9 was observed in AD across the three brain regions compared to the controls, suggesting their participation in AD pathogenesis. However, no important DNA methylation differences were observed, suggesting that other mechanism may be involved in controlling these genes expression.

Keywords: HSPA8; HSPA9; epigenetics; gene expression; mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / pathology
  • Analysis of Variance
  • Apolipoprotein E4 / genetics
  • Brain / metabolism
  • Brain / pathology*
  • Chi-Square Distribution
  • DNA Methylation / physiology*
  • Female
  • HSC70 Heat-Shock Proteins / genetics*
  • HSC70 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / genetics*
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*

Substances

  • Apolipoprotein E4
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • HSPA9 protein, human
  • Mitochondrial Proteins
  • RNA, Messenger