{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T13:37:41Z","timestamp":1776605861122,"version":"3.51.2"},"posted":{"date-parts":[[2026,4,19]]},"group-title":"In Review","reference-count":20,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,26]]},"abstract":"<title>Abstract<\/title>\n                <p>Neuroimmune signaling across the peripheral\u2013vascular\u2013glial axis is increasingly recognized as a driver of both age\u2011related brain vulnerability and the earliest stages of neurodegenerative disease, including Alzheimer disease. Evaluating this axis in vivo remains challenging due to limited neuroinflammatory imaging biomarkers. We utilized [11C]CS1P1 positron emission tomography (PET) to quantify sphingosine-1-phosphate receptor 1 (S1PR1) availability alongside plasma proteomics in 42 cognitively normal individuals (age 21-82). Through differential abundance analysis and structural equation modeling (SEM), we identified a multi-compartment neuroimmune cascade linking peripheral T-cell activation (CD40LG), vascular endothelial disruption (ICAM1\/TEK), central S1PR1 upregulation, and reactive astrogliosis (GFAP). Mediation analysis estimated this S1PR1 axis accounts for 25.5% of the total effect of CD40LG on GFAP. This cascade appears coupled to the astrocytic immune response and is exacerbated by underlying amyloid-beta pathology. These findings suggest [11C]CS1P1 may serve as an in vivo tool for evaluating peripheral-to-central immune crosstalk.<\/p>","DOI":"10.21203\/rs.3.rs-9237372\/v1","type":"posted-content","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T12:42:52Z","timestamp":1776602572000},"source":"Crossref","is-referenced-by-count":0,"title":["[11C]CS1P1 PET links T-cell\u2013associated immune activation with endothelial and astrocytic responses"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-0552","authenticated-orcid":false,"given":"Tammie","family":"Benzinger","sequence":"first","affiliation":[{"name":"Washington University in St. Louis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6092-857X","authenticated-orcid":false,"given":"Savannah Tiemann","family":"Powles","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hoagey","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaney","family":"Flores","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Friedrichsen","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Wu","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayashree","family":"Rajamanickam","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9735-5152","authenticated-orcid":false,"given":"Nelly","family":"Joseph-Mathurin","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Keefe","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine - 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