{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:24:50Z","timestamp":1786965890112,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,13]]},"group-title":"Geriatric Medicine","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH\/NIA","award":["R56AG063870"],"award-info":[{"award-number":["R56AG063870"]}]},{"name":"NIH\/NIA","award":["AG022304"],"award-info":[{"award-number":["AG022304"]}]},{"name":"NIH\/NIA","award":["U01AG073323"],"award-info":[{"award-number":["U01AG073323"]}]},{"name":"Jane and Lee Seidman Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) is characterized by amyloid beta and tau accumulation accompanied by altered inflammatory responses. Sex is an important modifier of AD risk and pathology, however, its influence on relationships between peripheral inflammatory markers and cerebrospinal fluid (CSF) AD biomarkers remains unclear. The aim of this study was to determine whether sex modifies peripheral inflammatory biomarker relationships associated with AD pathology and clinical stage.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>\n                    Twelve CSF biomarkers and 41 plasma biomarkers spanning AD pathology, neurodegeneration, and inflammation were measured on the Luminex platform in a cross-sectional cohort of 261 participants from the Cleveland Clinic Lou Ruvo Center for Brain Health Biobank. Associations were evaluated in sex-adjusted, sex-interaction, and sex-stratified models, accounting for age,\n                    <jats:italic>APOE<\/jats:italic>\n                    4 carrier status, and diagnosis.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Plasma IL-5 was inversely associated with clinical stage, and 10 plasma inflammatory markers, including Flt-3L, MCP-1, soluble TREM2 (sTREM2), TNF\u03b1, IL-8, IL-5, IL-12P40, IL-1RA, fractalkine, and G-CSF, were inversely associated with the CSF pTau181\/A\u03b242 ratio in pooled models adjusted for sex. Although formal biomarker \u00d7 sex interactions did not survive FDR correction, significant associations between the CSF pTau181\/A\u03b242 ratio and plasma MCP-1 and IL-12P40 were observed in females but not males.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Our findings identify a group of peripheral inflammatory markers associated with AD pathology and suggest that some of these relationships may vary by sex, warranting larger studies to clarify the role of sex in AD pathobiology.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.12.26360207","type":"posted-content","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T20:55:14Z","timestamp":1786654514000},"source":"Crossref","is-referenced-by-count":0,"title":["Plasma inflammatory biomarker associations with Alzheimer\u2019s disease clinical stage and CSF biomarkers: evaluation of sex effects"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-0803","authenticated-orcid":false,"given":"Rene","family":"Coig","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0454-5019","authenticated-orcid":false,"given":"Lavanya","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic Research, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1621-4711","authenticated-orcid":false,"given":"Maria","family":"Khrestian","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Tuason","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-7460","authenticated-orcid":false,"given":"Stephen","family":"Rao","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA"},{"name":"Center for Brain Health, Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6784-824X","authenticated-orcid":false,"given":"Jagan A.","family":"Pillai","sequence":"additional","affiliation":[{"name":"Imaging Institute, Cleveland Clinic, Cleveland, OH, USA"},{"name":"Neurological Institute, Cleveland Clinic, Cleveland, OH, USA"},{"name":"Department of Neurology, Cleveland Clinic, Cleveland, OH, 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