title: Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease.
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.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Ellison
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.|Department of Epidemiology, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Abner
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA.|Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lovell
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine
keywords: 5-hydroxymethylcytosine; 5-methylcytosine; Alzheimer's disease; epigenetic