Epigenetic changes in the progression of Alzheimer's disease

• Published in: Mechanisms of ageing and development 2013-10, Vol.134 (10), p.486-495
• Main Authors: Bradley-Whitman, M.A., Lovell, M.A.
• Format: Article
• Language: English
• Subjects: 5-Hydroxymethylcytosine; 5-Methylcytosine; Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Cerebellum - metabolism; Cerebellum - pathology; Epigenesis, Genetic; Female; Hippocampus - metabolism; Hippocampus - pathology; Humans; Male; Nerve Tissue Proteins - biosynthesis; Parahippocampal Gyrus - metabolism; Parahippocampal Gyrus - pathology; Preclinical Alzheimer's disease
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2013.08.005

•5hmC is more pronounced in nDNA than mtDNA or RNA.•Levels of 5mC and 5hmC are increased in PCAD and LAD HPG compared to NC HPG.•Levels of 5fC and 5caC are decreased in PCAD and LAD HPG compared to NC HPG.•Levels of TET1 are increased in PCAD and LAD HPG compared to NC HPG. 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