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To test the hypothesis that global levels of cytosine modification are altered throughout the progression of Alzheimer's disease, 5\u2010methylcytosine (5\u2010<jats:styled-content style=\"fixed-case\">mC<\/jats:styled-content>) and 5\u2010hydroxymethylcytosine (5\u2010hmC) were quantified using gas chromatography\/mass spectrometry (<jats:styled-content style=\"fixed-case\">GC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>) and stable labeled internal standards of cytosine, 5\u2010<jats:styled-content style=\"fixed-case\">mC<\/jats:styled-content>, and 5\u2010hmC. Cytosine modifications were quantified in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> 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 (<jats:styled-content style=\"fixed-case\">NC<\/jats:styled-content>) subjects and subjects with mild cognitive impairment (<jats:styled-content style=\"fixed-case\">MCI<\/jats:styled-content>), preclinical Alzheimer's disease (<jats:styled-content style=\"fixed-case\">PCAD<\/jats:styled-content>), late onset Alzheimer's disease, frontotemporal lobar degeneration (<jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content>) and dementia with Lewy bodies (<jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>). Repeated measures analyses of the data show significant alterations in 5\u2010<jats:styled-content style=\"fixed-case\">mC<\/jats:styled-content> and 5\u2010hmC in early stages of Alzheimer's disease (<jats:styled-content style=\"fixed-case\">PCAD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MCI<\/jats:styled-content>), as well as <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content> 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 <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> as well as other types of neurodegeneration.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13912-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13912","type":"journal-article","created":{"date-parts":[[2016,11,27]],"date-time":"2016-11-27T09:12:38Z","timestamp":1480237958000},"page":"383-394","source":"Crossref","is-referenced-by-count":57,"title":["Multiregional analysis of global 5\u2010methylcytosine and 5\u2010hydroxymethylcytosine throughout the progression of Alzheimer's disease"],"prefix":"10.1111","volume":"140","author":[{"given":"Elizabeth M.","family":"Ellison","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin L.","family":"Abner","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging University of Kentucky Lexington Kentucky USA"},{"name":"Department of Epidemiology University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Kentucky Lexington Kentucky USA"},{"name":"Sanders\u2010Brown Center on Aging University of Kentucky Lexington Kentucky 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