{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T08:53:43Z","timestamp":1768985623695,"version":"3.49.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K10318"],"award-info":[{"award-number":["17K10318"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K10317"],"award-info":[{"award-number":["17K10317"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mitsui Life Social Welfare Foundation"},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18dk0207025h0003"],"award-info":[{"award-number":["18dk0207025h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Private University Research Branding Project from the Ministry of Education, Culture, Sports, Science and Technology"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Early diagnosis of dementia including Alzheimer\u2019s disease (AD) is an urgent medical and welfare issue. However, to date, no simple biometrics have been available. We reported that blood DNA methylation levels of the <jats:italic>COASY<\/jats:italic> gene, which encodes coenzyme A synthase, were increased in individuals with AD and amnestic mild cognitive impairment (aMCI). The present study sought to replicate these findings with larger numbers of samples. Another objective was to clarify whether <jats:italic>COASY<\/jats:italic> methylation is associated with neurodegeneration through a comparison of AD, AD with cardiovascular disease (CVD), and vascular dementia (VaD). We measured blood <jats:italic>COASY<\/jats:italic> methylation levels in normal controls (NCs) (<jats:italic>n<\/jats:italic>\u2009=\u2009200), and individuals with aMCI (<jats:italic>n<\/jats:italic>\u2009=\u200922), AD (<jats:italic>n<\/jats:italic>\u2009=\u2009151), and VaD (<jats:italic>n<\/jats:italic>\u2009=\u200921). Compared with NCs, they were significantly higher in individuals with aMCI and AD. Further, they were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them. These findings suggest that <jats:italic>COASY<\/jats:italic> methylation levels may be related to neurodegeneration in AD.<\/jats:p>","DOI":"10.1038\/s41598-020-69248-9","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T10:07:35Z","timestamp":1595412455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Increased blood COASY DNA methylation levels a potential biomarker for early pathology of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"10","author":[{"given":"Nobuyuki","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunichiro","family":"Shinagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidehito","family":"Niimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Kida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Tagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Oka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Shikimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Noda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Mimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Shigeta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,22]]},"reference":[{"key":"69248_CR1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimer\u2019s Dementia J. Alzheimer\u2019s Assoc. 7, 263\u2013269. https:\/\/doi.org\/10.1016\/j.jalz.2011.03.005 (2011).","journal-title":"Alzheimer's Dementia J. Alzheimer's Assoc."},{"key":"69248_CR2","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1016\/S0140-6736(15)00463-8","volume":"386","author":"JT O'Brien","year":"2015","unstructured":"O\u2019Brien, J. T. & Thomas, A. Vascular dementia. Lancet 386, 1698\u20131706. https:\/\/doi.org\/10.1016\/S0140-6736(15)00463-8 (2015).","journal-title":"Lancet"},{"key":"69248_CR3","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe, D. J. & Hardy, J. The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Mol. Med. 8, 595\u2013608. https:\/\/doi.org\/10.15252\/emmm.201606210 (2016).","journal-title":"EMBO Mol. Med."},{"key":"69248_CR4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nrg3142","volume":"13","author":"R Feil","year":"2012","unstructured":"Feil, R. & Fraga, M. F. Epigenetics and the environment: emerging patterns and implications. Nat. Rev. Genet. 13, 97\u2013109. https:\/\/doi.org\/10.1038\/nrg3142 (2012).","journal-title":"Nat. Rev. Genet."},{"key":"69248_CR5","doi-asserted-by":"publisher","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","volume":"14","author":"S Horvath","year":"2013","unstructured":"Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol. 14, R115. https:\/\/doi.org\/10.1186\/gb-2013-14-10-r115 (2013).","journal-title":"Genome Biol."},{"key":"69248_CR6","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.molcel.2012.10.016","volume":"49","author":"G Hannum","year":"2013","unstructured":"Hannum, G. et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell 49, 359\u2013367. https:\/\/doi.org\/10.1016\/j.molcel.2012.10.016 (2013).","journal-title":"Mol. Cell"},{"key":"69248_CR7","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jalz.2017.10.002","volume":"14","author":"PD Fransquet","year":"2018","unstructured":"Fransquet, P. D. et al. Blood DNA methylation as a potential biomarker of dementia: a systematic review. Alzheimer\u2019s Dementia J. Alzheimer\u2019s Assoc. 14, 81\u2013103. https:\/\/doi.org\/10.1016\/j.jalz.2017.10.002 (2018).","journal-title":"Alzheimer's Dementia J. Alzheimer's Assoc."},{"key":"69248_CR8","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.ajhg.2013.11.008","volume":"94","author":"S Dusi","year":"2014","unstructured":"Dusi, S. et al. Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. Am. J. Hum. Genet. 94, 11\u201322. https:\/\/doi.org\/10.1016\/j.ajhg.2013.11.008 (2014).","journal-title":"Am. J. Hum. Genet."},{"key":"69248_CR9","doi-asserted-by":"publisher","first-page":"361218","DOI":"10.1155\/2012\/361218","volume":"2012","author":"JH Lee","year":"2012","unstructured":"Lee, J. H. et al. Polymorphisms in HSD17B1: early onset and increased risk of Alzheimer\u2019s disease in women with down syndrome. Curr. Gerontol. Geriatr. Res. 2012, 361218. https:\/\/doi.org\/10.1155\/2012\/361218 (2012).","journal-title":"Curr. Gerontol. Geriatr. Res."},{"key":"69248_CR10","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1038\/s41467-018-03422-6","volume":"9","author":"CC Lin","year":"2018","unstructured":"Lin, C. C. et al. CoA synthase regulates mitotic fidelity via CBP-mediated acetylation. Nat. Commun. 9, 1039. https:\/\/doi.org\/10.1038\/s41467-018-03422-6 (2018).","journal-title":"Nat. Commun."},{"key":"69248_CR11","doi-asserted-by":"publisher","first-page":"e41","DOI":"10.1093\/nar\/gkm013","volume":"35","author":"TK Wojdacz","year":"2007","unstructured":"Wojdacz, T. K. & Dobrovic, A. Methylation-sensitive high resolution melting (MS-HRM): a new approach for sensitive and high-throughput assessment of methylation. Nucl. Acids Res. 35, e41. https:\/\/doi.org\/10.1093\/nar\/gkm013 (2007).","journal-title":"Nucl. Acids Res."},{"key":"69248_CR12","doi-asserted-by":"publisher","first-page":"e0146449","DOI":"10.1371\/journal.pone.0146449","volume":"11","author":"N Kobayashi","year":"2016","unstructured":"Kobayashi, N. et al. Development of biomarkers based on DNA methylation in the NCAPH2\/LMF2 promoter region for diagnosis of alzheimer\u2019s disease and amnesic mild cognitive impairment. PLoS ONE 11, e0146449. https:\/\/doi.org\/10.1371\/journal.pone.0146449 (2016).","journal-title":"PLoS ONE"},{"key":"69248_CR13","doi-asserted-by":"publisher","first-page":"e0168816","DOI":"10.1371\/journal.pone.0168816","volume":"11","author":"N Kobayashi","year":"2016","unstructured":"Kobayashi, N. et al. Usefulness of DNA methylation levels in COASY and SPINT1 gene promoter regions as biomarkers in diagnosis of alzheimer\u2019s disease and amnestic mild cognitive impairment. PLoS ONE 11, e0168816. https:\/\/doi.org\/10.1371\/journal.pone.0168816 (2016).","journal-title":"PLoS ONE"},{"key":"69248_CR14","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1159\/000339358","volume":"33","author":"T Nagata","year":"2012","unstructured":"Nagata, T., Shinagawa, S., Nukariya, K., Yamada, H. & Nakayama, K. Association between BDNF polymorphism (Val66Met) and executive function in patients with amnestic mild cognitive impairment or mild Alzheimer disease. Dement. Geriatr. Cogn. Disord. 33, 266\u2013272. https:\/\/doi.org\/10.1159\/000339358 (2012).","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"69248_CR15","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1001\/archneur.58.12.1985","volume":"58","author":"RC Petersen","year":"2001","unstructured":"Petersen, R. C. et al. Current concepts in mild cognitive impairment. Arch. Neurol. 58, 1985\u20131992 (2001).","journal-title":"Arch. Neurol."},{"key":"69248_CR16","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1212\/WNL.34.7.939","volume":"34","author":"G McKhann","year":"1984","unstructured":"McKhann, G. et al. Clinical diagnosis of Alzheimer\u2019s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer\u2019s Disease. Neurology 34, 939\u2013944 (1984).","journal-title":"Neurology"},{"key":"69248_CR17","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/j.1749-6632.2002.tb04807.x","volume":"977","author":"AD Korczyn","year":"2002","unstructured":"Korczyn, A. D. Mixed dementia\u2013the most common cause of dementia. Ann. N. Y. Acad. Sci. 977, 129\u2013134. https:\/\/doi.org\/10.1111\/j.1749-6632.2002.tb04807.x (2002).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"69248_CR18","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1212\/wnl.43.2.250","volume":"43","author":"GC Roman","year":"1993","unstructured":"Roman, G. C. et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43, 250\u2013260. https:\/\/doi.org\/10.1212\/wnl.43.2.250 (1993).","journal-title":"Neurology"},{"key":"69248_CR19","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12981","author":"H Kida","year":"2020","unstructured":"Kida, H. et al. Approach-oriented coping strategy level may be related to volume of the whole hippocampus in the elderly. Psychiatry Clin. Neurosci. https:\/\/doi.org\/10.1111\/pcn.12981 (2020).","journal-title":"Psychiatry Clin. Neurosci."},{"key":"69248_CR20","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein, M. F., Folstein, S. E. & McHugh, P. R. \u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatry Res. 12, 189\u2013198 (1975).","journal-title":"J. Psychiatry Res."},{"key":"69248_CR21","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1080\/08952841.2015.1018038","volume":"28","author":"JG Ronquillo","year":"2016","unstructured":"Ronquillo, J. G., Baer, M. R. & Lester, W. T. Sex-specific patterns and differences in dementia and Alzheimer\u2019s disease using informatics approaches. J. Women Aging 28, 403\u2013411. https:\/\/doi.org\/10.1080\/08952841.2015.1018038 (2016).","journal-title":"J. Women Aging"},{"key":"69248_CR22","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3233\/JAD-180213","volume":"67","author":"AM Medeiros","year":"2019","unstructured":"Medeiros, A. M. & Silva, R. H. Sex differences in Alzheimer\u2019s disease: where do we stand?. J. Alzheimers. Dis. 67, 35\u201360. https:\/\/doi.org\/10.3233\/JAD-180213 (2019).","journal-title":"J. Alzheimers. Dis."},{"key":"69248_CR23","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","volume":"9","author":"CR Jack Jr","year":"2010","unstructured":"Jack, C. R. Jr. et al. Hypothetical model of dynamic biomarkers of the Alzheimer\u2019s pathological cascade. Lancet Neurol. 9, 119\u2013128. https:\/\/doi.org\/10.1016\/S1474-4422(09)70299-6 (2010).","journal-title":"Lancet Neurol."},{"key":"69248_CR24","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/978-1-4939-7481-8_28","volume":"1708","author":"D Hussmann","year":"2018","unstructured":"Hussmann, D. & Hansen, L. L. Methylation-sensitive high resolution melting (MS-HRM). Methods Mol. Biol. 1708, 551\u2013571. https:\/\/doi.org\/10.1007\/978-1-4939-7481-8_28 (2018).","journal-title":"Methods Mol. Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69248-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69248-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69248-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T14:54:40Z","timestamp":1670338480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69248-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,22]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["69248"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-69248-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,22]]},"assertion":[{"value":"24 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"K.K. has stock in Virus Ikagaku Kenkyusho Inc. However, Virus Ikagaku Kenkyusho Inc. was not involved in the design of the study or conducting it; in the collection, management, analysis, and interpretation of the data; or in the preparation, review and approval of the manuscript. The other authors report no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12217"}}