{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:33:31Z","timestamp":1787592811070,"version":"build-2736575974"},"reference-count":73,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","award":["AS\u2010PG\u201014\u2010038"],"award-info":[{"award-number":["AS\u2010PG\u201014\u2010038"]}],"id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG067015"],"award-info":[{"award-number":["R01AG067015"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011878","name":"Vlaamse regering","doi-asserted-by":"publisher","award":["VIND IWT 135043"],"award-info":[{"award-number":["VIND IWT 135043"]}],"id":[{"id":"10.13039\/501100011878","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["#12Y1620N"],"award-info":[{"award-number":["#12Y1620N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["#320030_141179"],"award-info":[{"award-number":["#320030_141179"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_204886"],"award-info":[{"award-number":["320030_204886"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2022\u201001018"],"award-info":[{"award-number":["#2022\u201001018"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2017\u201000915"],"award-info":[{"award-number":["#2017\u201000915"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2019\u201002397"],"award-info":[{"award-number":["#2019\u201002397"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007436","name":"Familjen Erling-Perssons Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007436","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010815","name":"Stiftelsen f\u00f6r Gamla Tj\u00e4narinnor","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010815","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","award":["#FO2022\u20100270"],"award-info":[{"award-number":["#FO2022\u20100270"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["UKDRI\u20101003"],"award-info":[{"award-number":["UKDRI\u20101003"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["SG\u201023\u20101038904 QC"],"award-info":[{"award-number":["SG\u201023\u20101038904 QC"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>We investigated blood DNA methylation patterns associated with 15 well\u2010established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF\u2010AD) study using the EPIC array.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We identified Bonferroni\u2010significant differential methylation associated with CSF YKL\u201040 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL\u201040 levels correlating with plasma YKL\u201040 levels. A co\u2010localization analysis showed shared genetic variants underlying YKL\u201040 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co\u2010methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      We conducted the most comprehensive epigenome\u2010wide association study (EWAS) of AD\u2010relevant CSF biomarkers to date. Future work should explore the relationship between\n                      <jats:italic>YKL\u201040<\/jats:italic>\n                      genotype, DNA methylation, and protein levels in the brain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Blood DNA methylation was assessed in the EMIF\u2010AD MBD study.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Epigenome\u2010wide association studies (EWASs) were performed for 15 Alzheimer's disease (AD)\u2013relevant cerebrospinal fluid (CSF) biomarker measures.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Five Bonferroni\u2010significant loci were associated with YKL\u201040 levels and seven with neurofilament light chain (NfL).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            DNA methylation in\n                            <jats:italic>YKL\u201040<\/jats:italic>\n                            co\u2010localized with previously reported genetic variation.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            DNA methylation potentially mediates the effect of\u00a0single\u2010nucleotide polymorphisms (SNPs) in\n                            <jats:italic>YKL\u201040<\/jats:italic>\n                            on CSF protein levels.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14098","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T07:00:20Z","timestamp":1724828420000},"page":"6722-6739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF\u2010AD study"],"prefix":"10.1002","volume":"20","author":[{"given":"Rebecca G.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter  Exeter Devon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Pishva","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter  Exeter Devon UK"},{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences (FHML) Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morteza","family":"Kouhsar","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter  Exeter Devon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Imm","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter  Exeter Devon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerija","family":"Dobricic","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics (LIGA) University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Johannsen","sequence":"additional","affiliation":[{"name":"Danish Dementia Research Centre, Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wittig","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology Christian\u2010Albrechts\u2010University of Kiel Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology Christian\u2010Albrechts\u2010University of Kiel Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology KU Leuven, Leuven Brain Institute Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien","family":"Schaeverbeke","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology KU Leuven, Leuven Brain Institute Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Freund\u2010Levi","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education S\u00f6dersjukhuset, Karolinska Institutet Stockholm Sweden"},{"name":"School of Medical Sciences \u00d6rebro University \u00d6rebro Sweden"},{"name":"Department of Geriatrics S\u00f6dert\u00e4lje Hospital S\u00f6dert\u00e4lje Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Fr\u00f6lich","sequence":"additional","affiliation":[{"name":"Department of Geriatric Psychiatry Central Institut of Mental Health Medical Faculty Mannheim\/Heidelberg University Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Scheltens","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory Department of Laboratory Medicine, Amsterdam Neuroscience Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Frisoni","sequence":"additional","affiliation":[{"name":"Memory center Geneva University and University Hospitals; on behalf of the AMYPAD consortium Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Blin","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille University\u2010CNRS Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill C.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Neuroscience Therapeutic Area, GlaxoSmithKline R&amp;D Stevenage Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9gis","family":"Bordet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille Lille Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan","family":"Engelborghs","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Antwerp Antwerp Belgium"},{"name":"Neuroprotection &amp; Neuromodulation (NEUR) Research Group, Center for Neurosciences (C4N) Vrije Universiteit Brussel (VUB), Jette Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"de Roeck","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Martinez\u2010Lage","sequence":"additional","affiliation":[{"name":"Center for Research and Advanced Therapies Fundaci\u00f3n CITA\u2010Alzh\u00e9imer Fundazioa San Sebastian Gipuzkoa Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miren","family":"Altuna","sequence":"additional","affiliation":[{"name":"Center for Research and Advanced Therapies Fundaci\u00f3n CITA\u2010Alzh\u00e9imer Fundazioa San Sebastian Gipuzkoa Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikel","family":"Tainta","sequence":"additional","affiliation":[{"name":"Center for Research and Advanced Therapies Fundaci\u00f3n CITA\u2010Alzh\u00e9imer Fundazioa San Sebastian Gipuzkoa Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Lle\u00f3","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) Hospital Sant Pau Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Sala","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) Hospital Sant Pau Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Popp","sequence":"additional","affiliation":[{"name":"University Hospital of Psychiatry Z\u00fcrich, University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendoline","family":"Peyratout","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University Hospital of Lausanne (CHUV) Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Winchester","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejo","family":"Nevado\u2010Holgado","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Verhey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences (FHML) Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Tsolaki","sequence":"additional","affiliation":[{"name":"1st Department of Neurology School of Medicine Laboratory of Neurodegenerative Diseases Center for Interdisciplinary Research and Innovation Aristotle University of Thessaloniki, and Alzheimer Hellas Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Andreasson","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg G\u00f6teborg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg G\u00f6teborg Sweden"},{"name":"Paris Brain Institute ICM, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Sorbonne University Paris France"},{"name":"Neurodegenerative Disorder Research Center Division of Life Sciences and Medicine and Department of Neurology Institute on Aging and Brain Disorders University of Science and Technology of China and First Affiliated Hospital of USTC Hefei PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg G\u00f6teborg Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology Queen Square London UK"},{"name":"UK Dementia Research Institute at UCL London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases, N.T. Shatin Hong Kong China"},{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health, University of Wisconsin\u2010Madison Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Streffer","sequence":"additional","affiliation":[{"name":"Translational Medicine Neuroscience UCB Biopharma SRL Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J. B.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences (FHML) Maastricht University  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lovestone","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University Hospital of Lausanne (CHUV) Lausanne Switzerland"},{"name":"Currently at: Johnson &amp; Johnson Innovative Medicines Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter Jelle","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences (FHML) Maastricht University  Maastricht The Netherlands"},{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience Vrije Universiteit Amsterdam, Amsterdam UMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bertram","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics (LIGA) University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-6065","authenticated-orcid":false,"given":"Katie","family":"Lunnon","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter  Exeter Devon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"World Health Organization (2012). 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