Multiregional analysis of global 5‐methylcytosine and 5‐hydroxymethylcytosine throughout the progression of Alzheimer's disease. Issue 3 (February 2017)

• Record Type: Journal Article
• Authors: Ellison, Elizabeth M.; Abner, Erin L.; Lovell, Mark A.
• Is Part Of: Journal of neurochemistry. Volume 140:Issue 3(2017)
• Page Start: 383
• Page End: 394
• Publication Date: 2017-02
• Subjects: 5‐hydroxymethylcytosine -- 5‐methylcytosine -- Alzheimer's disease -- epigenetic; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13912
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract : Cytosine modifications can alter transcriptional states and may play a role in Alzheimer's disease (AD). DNA from AD affected brain regions was analyzed using gas chromatography mass spectrometry for normal aging, preclinical AD (PCAD), mild cognitive impairment (MCI), late onset AD (LOAD), frontotemporal lobar degeneration (FTLD), and dementia with Lewy bodies (DLB) subjects. Alterations in 5‐methylcytosine (5‐mC) and 5‐hydroxymethylcytosine (5‐hmC) were seen in early stages of AD, indicating a possible role of epigenetic modification in AD progression. Abstract: Epigenetic modifications to cytosine are known to alter transcriptional states and deregulate gene expression in cancer, embryonic development, and most recently in neurodegeneration. To test the hypothesis that global levels of cytosine modification are altered throughout the progression of Alzheimer's disease, 5‐methylcytosine (5‐mC) and 5‐hydroxymethylcytosine (5‐hmC) were quantified using gas chromatography/mass spectrometry (GC/MS) and stable labeled internal standards of cytosine, 5‐mC, and 5‐hmC. Cytosine modifications were quantified in DNA extracted from tissue specimens of four brain regions (cerebellum, inferior parietal lobe, superior and middle temporal gyrus, and hippocampus/parahippocampal gyrus) of cognitively normal control (NC) subjects and subjects with mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late onset Alzheimer's disease, frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). Repeated measures analyses of the data show significant alterations in 5‐mC and 5‐hmC in early stages of Alzheimer's disease (PCAD and MCI), as well as FTLD and DLB subjects, across multiple regions of the brain. These data suggest alterations in epigenetic regulation of genes may play an early role in the progression of AD as well as other types of neurodegeneration.