Epigenetic changes in the progression of Alzheimer's disease

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

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


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
Issue number10
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.


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

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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