{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T12:00:57Z","timestamp":1771156857080,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Epigenetic mechanisms act as mediators of genetic and environmental influences. In Alzheimer's disease, blood\u2010based DNA methylation signatures are increasingly being explored as minimally invasive peripheral biomarkers. We previously reported associations between blood DNA methylation in the\n                    <jats:italic>CHI3L1<\/jats:italic>\n                    gene (encoding YKL\u201040) and cerebrospinal fluid (CSF) levels of YKL\u201040, a marker of neuroinflammation. These findings have now been replicated in an independent study (Kaleck et\u00a0al. 2025), reinforcing their robustness and biological relevance. We also reported associations between DNA methylation and CSF neurofilament light chain levels, a marker of axonal damage, which were not independently replicated in the analyses by Kaleck et\u00a0al. Several factors may have contributed to this inconsistency in results, which we discuss in detail as they are relevant to future DNA methylation\u2010based studies in the field. Together, these findings highlight both the potential and the complexity of identifying consistent blood\u2010based epigenomic signatures for neurodegenerative processes. They also underscore the importance of harmonizing methodologies across studies to improve reproducibility and, eventually, to yield meaningful biomarkers allowing an early detection of this devastating disease.\n                  <\/jats:p>","DOI":"10.1002\/alz.70646","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T04:25:42Z","timestamp":1756873542000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Delineating blood DNA methylation biomarkers for Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Ehsan","family":"Pishva","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Sciences Faculty of Health and Life Sciences University of Exeter  Exeter 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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Bertram","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics (LIGA) University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"e_1_2_1_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3786"},{"key":"e_1_2_1_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3782"},{"key":"e_1_2_1_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010019\u20100755\u20105"},{"key":"e_1_2_1_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010019\u20100636\u2010y"},{"key":"e_1_2_1_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.017"},{"key":"e_1_2_1_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.01.001"},{"key":"e_1_2_1_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14501"},{"key":"e_1_2_1_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010023\u201001232\u20107"},{"key":"e_1_2_1_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010020\u201000944\u2010z"},{"key":"e_1_2_1_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13072\u2010018\u20100211\u20103"},{"key":"e_1_2_1_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010015\u20100258\u20108"},{"key":"e_1_2_1_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023243\u20104"},{"key":"e_1_2_1_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201033394\u20107"},{"key":"e_1_2_1_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201019791\u2010w"},{"key":"e_1_2_1_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.06.023"},{"key":"e_1_2_1_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010021\u201001179\u20102"},{"key":"e_1_2_1_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010020\u201000864\u2010y"},{"key":"e_1_2_1_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14496"},{"key":"e_1_2_1_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14098"},{"key":"e_1_2_1_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010023\u201001216\u20107"},{"key":"e_1_2_1_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(16)00070\u20103"},{"key":"e_1_2_1_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70647"},{"key":"e_1_2_1_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010020\u201001074\u2010z"},{"key":"e_1_2_1_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010024\u201000955\u2010x"},{"key":"e_1_2_1_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470743386"},{"key":"e_1_2_1_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4088"},{"key":"e_1_2_1_8_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.3037"},{"key":"e_1_2_1_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201014\u2010293"},{"key":"e_1_2_1_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07331"},{"key":"e_1_2_1_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201052937\u20108"}],"container-title":["Alzheimer's &amp; 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