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 language | English |
|---|---|
| Pages (from-to) | 486-495 |
| Number of pages | 10 |
| Journal | Mechanisms of Ageing and Development |
| Volume | 134 |
| Issue number | 10 |
| DOIs | |
| State | Published - 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