Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease

Elizabeth M. Ellison, Erin L. Abner, Mark A. Lovell

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Epigenetic modifications to cytosine are known to alter transcriptional states and deregulate gene expression in cancer, embryonic development, and most recently in neurodegeneration. To test the hypothesis that global levels of cytosine modification are altered throughout the progression of Alzheimer's disease, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) were quantified using gas chromatography/mass spectrometry (GC/MS) and stable labeled internal standards of cytosine, 5-mC, and 5-hmC. Cytosine modifications were quantified in DNA extracted from tissue specimens of four brain regions (cerebellum, inferior parietal lobe, superior and middle temporal gyrus, and hippocampus/parahippocampal gyrus) of cognitively normal control (NC) subjects and subjects with mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late onset Alzheimer's disease, frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). Repeated measures analyses of the data show significant alterations in 5-mC and 5-hmC in early stages of Alzheimer's disease (PCAD and MCI), as well as FTLD and DLB subjects, across multiple regions of the brain. These data suggest alterations in epigenetic regulation of genes may play an early role in the progression of AD as well as other types of neurodegeneration. (Figure presented.).

Original languageEnglish
Pages (from-to)383-394
Number of pages12
JournalJournal of Neurochemistry
Volume140
Issue number3
DOIs
StatePublished - Feb 1 2017

Bibliographical note

Publisher Copyright:
© 2016 International Society for Neurochemistry

Keywords

  • 5-hydroxymethylcytosine
  • 5-methylcytosine
  • Alzheimer's disease
  • epigenetic

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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