Epigenetic changes in the progression of Alzheimer's disease

M. A. Bradley-Whitman, M. A. Lovell

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA demethylation, is driven by the ten eleven translocation (TET) family of proteins that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer's disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age-matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage AD (LAD) subjects by immunochemistry. The results showed significantly (p<. 0.05) increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In contrast, levels of 5fC and 5caC were significantly (p<. 0.05) decreased in the HPG of PCAD and LAD subjects. Overall, the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.

Original languageEnglish
Pages (from-to)486-495
Number of pages10
JournalMechanisms of Ageing and Development
Volume134
Issue number10
DOIs
StatePublished - Oct 2013

Bibliographical note

Funding Information:
This research was supported by NIH grants 5P01-AG05119 and P30-AG028383 . The authors thank the UK-ADC Clinical, Neuropathology and Biostatistics Cores for tissue procurement and neuropathologic data. The authors also thank Ms. Sonya Anderson for subject demographic data and Ms. Paula Thomason for editorial assistance.

Keywords

  • 5-Hydroxymethylcytosine
  • 5-Methylcytosine
  • Alzheimer's disease
  • Preclinical Alzheimer's disease

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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