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To investigate levels of nucleic acid oxidation in both early and late stages of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>, levels of multiple base adducts were quantified in nuclear and mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> from the superior and middle temporal gyri (<jats:styled-content style=\"fixed-case\">SMTG<\/jats:styled-content>), inferior parietal lobule (<jats:styled-content style=\"fixed-case\">IPL<\/jats:styled-content>), and cerebellum (<jats:styled-content style=\"fixed-case\">CER<\/jats:styled-content>) of age\u2010matched normal control subjects, subjects with mild cognitive impairment, preclinical <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>, late\u2010stage <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>, and non\u2010<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> neurological disorders (diseased control; <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content>) using gas chromatography\/mass spectrometry. Median levels of multiple <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> adducts in nuclear and mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> were significantly (<jats:italic>p\u00a0\u2264\u00a0<\/jats:italic>0.05) elevated in the <jats:styled-content style=\"fixed-case\">SMTG<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> IPL<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">CER<\/jats:styled-content> in multiple stages of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> and in <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content> subjects. Elevated levels of fapyguanine and fapyadenine in mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> suggest a hypoxic environment early in the progression of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> and in <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content> subjects. Overall, these data suggest that oxidative damage is an early event not only in the pathogenesis of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> but is also present in neurodegenerative diseases in general.\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\/jnc12444-fig-0002-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Levels of oxidized nucleic acids in nDNA and mtDNA were found to be significantly elevated in mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late\u2010stage AD (LAD), and a pooled diseased control group (DC) of frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB) subjects compared to normal control (NC) subjects. Nucleic acid oxidation peaked early in disease progression and remained elevated. The study suggests nucleic acid oxidation is a general event in neurodegeneration.<\/jats:p>","DOI":"10.1111\/jnc.12444","type":"journal-article","created":{"date-parts":[[2013,9,7]],"date-time":"2013-09-07T05:55:50Z","timestamp":1378533350000},"page":"294-304","source":"Crossref","is-referenced-by-count":102,"title":["Nucleic acid oxidation: an early feature of Alzheimer's disease"],"prefix":"10.1111","volume":"128","author":[{"given":"Melissa A.","family":"Bradley\u2010Whitman","sequence":"first","affiliation":[{"name":"Sanders\u2010Brown Center on Aging and Alzheimer's Disease Center University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Timmons","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina L.","family":"Beckett","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging and Alzheimer's Disease Center University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging and Alzheimer's Disease Center University of Kentucky Lexington Kentucky USA"},{"name":"Department of Molecular and Cellular Biochemistry University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert C.","family":"Lynn","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging and Alzheimer's Disease Center University of Kentucky Lexington Kentucky USA"},{"name":"Department of Chemistry University of Kentucky Lexington Kentucky USA"},{"name":"University of Kentucky Mass Spectrometry Facility University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Sanders\u2010Brown Center on Aging and Alzheimer's Disease Center University of Kentucky Lexington Kentucky USA"},{"name":"Department of Chemistry University of Kentucky Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1084-8592(97)80038-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.7915"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200103260-00045"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.05.018"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(89)90197-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.02.016"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.08.016"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2003.09.001"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0237-2"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/18.9.1833"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0752rev"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9536025"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1515\/znc-1999-3-414"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"8532","DOI":"10.1523\/JNEUROSCI.23-24-08532.2003","article-title":"Amyloid\u2010beta immunization effectively reduces amyloid deposition in FcRgamma\u2010\/\u2010 knock\u2010out mice","volume":"23","author":"Das P.","year":"2003","journal-title":"J. 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