Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain

Daniel Condliffe, Andrew Wong, Claire Troakes, Petroula Proitsi, Yogen Patel, Leonidas Chouliaras, Cathy Fernandes, Jonathan Cooper, Simon Lovestone, Leonard Schalkwyk, Jonathan Mill, Katie Lunnon

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Epigenetic processes play a key role in the central nervous system and altered levels of 5-methylcytosine have been associated with a number of neurologic phenotypes, including Alzheimer's disease (AD). Recently, 3 additional cytosine modifications have been identified (5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine), which are thought to be intermediate steps in the demethylation of 5-methylcytosine to unmodified cytosine. Little is known about the frequency of these modifications in the human brain during health or disease. In this study, we used immunofluorescence to confirm the presence of each modification in human brain and investigate their cross-tissue abundance in AD patients and elderly control samples. We identify a significant AD-associated decrease in global 5-hydroxymethylcytosine in entorhinal cortex and cerebellum, and differences in 5-formylcytosine levels between brain regions. Our study further implicates a role for epigenetic alterations in AD.

Original languageEnglish
Pages (from-to)1850-1854
Number of pages5
JournalNeurobiology of Aging
Volume35
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • 5-caC
  • 5-carboxylcytosine
  • 5-fC
  • 5-formylcytosine
  • 5-hmC
  • 5-hydroxymethylcytosine
  • 5-mC
  • 5-methylcytosine
  • Alzheimer's disease
  • Brain
  • DNA methylation
  • Epigenetics

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