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

NEUROBIOLOGY OF AGING

卷:35

Article

Condliffe, Daniel¹  Wong, Andrew¹  Troakes, Claire¹  Proitsi, Petroula¹  Patel, Yogen¹  Chouliaras, Leonidas²  Fernandes, Cathy¹  Cooper, Jonathan¹  Lovestone, Simon¹  Schalkwyk, Leonard¹  Mill, Jonathan^1,3  Lunnon, Katie³ 

[1] Kings Coll London, Inst Psychiat, London, England

[2] Maastricht Univ, Med Ctr, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands

[3] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England

关键词: Epigenetics;    DNA methylation;    Brain;    5-methylcytosine;    5-mC;    5-hydroxymethylcytosine;    5-hmC;    5-formylcytosine;    5-fC;    5-carboxylcytosine;    5-caC;    Alzheimer's disease;   

DOI  :  10.1016/j.neurobiolaging.2014.02.002

来源: Elsevier

【 摘 要 】

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. (C) 2014 Elsevier Inc. All rights reserved.

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