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To identify sex-specific differentially methylated positions (DMPs) and genes in persons with mild cognitive impairment (MCI) and AD, we analyzed whole genome methylation sequencing on blood samples from participants with MCI (N=99, 52% female), AD (N=109, 43% female), and those cognitively unimpaired (CU; N=174, 52% female). Ninety-four percent of DMPs from MCI\n                  <jats:italic>vs<\/jats:italic>\n                  . CU, AD\n                  <jats:italic>vs<\/jats:italic>\n                  . CU, and AD\n                  <jats:italic>vs<\/jats:italic>\n                  . MCI pairwise comparisons were sex-specific. Female-specific DMPs were enriched in neurologic gene sets (\n                  <jats:italic>e.g<\/jats:italic>\n                  ., synaptic membrane, ion channel complex), while male-specific DMPs showed limited enrichment. Sex-specific DMPs overlapped blood-specific enhancers, promoters, and transcription factor binding motifs, highlighting divergent epigenetic regulation by sex. These findings identify sex-specific genes and molecular pathways in MCI and AD and support that blood DNA methylation levels can distinguish cognitive status.\n                <\/jats:p>","DOI":"10.1101\/2025.05.15.654279","type":"posted-content","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T11:05:14Z","timestamp":1747652714000},"source":"Crossref","is-referenced-by-count":1,"title":["Sex-Specific Differential DNA Methylation in Mild Cognitive Impairment and Alzheimer\u2019s Disease"],"prefix":"10.64898","author":[{"given":"Phillip E.","family":"Bergmann","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Madrid","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ligia A.","family":"Papale","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay R.","family":"Clark","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 600 Highland Ave, Madison, WI 53792, USA"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Asthana","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 600 Highland Ave, Madison, WI 53792, USA"},{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 600 Highland Ave, Madison, WI 53792, USA"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"},{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-0922","authenticated-orcid":false,"given":"S\u00fcnd\u00fcz","family":"Kele\u015f","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Wisconsin, Medical Sciences Center, 1300 University Ave Room 1220, Madison, WI 53706 USA"},{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirk J.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Institute, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"},{"name":"Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0637-4137","authenticated-orcid":false,"given":"Reid S.","family":"Alisch","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041122361553000_2025.05.15.654279v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12362"},{"key":"2026041122361553000_2025.05.15.654279v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1920-1"},{"key":"2026041122361553000_2025.05.15.654279v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00619-0"},{"key":"2026041122361553000_2025.05.15.654279v1.4","doi-asserted-by":"crossref","unstructured":"Sarica, A. et al. 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