{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:01:24Z","timestamp":1790402484632,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":84,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Elevated cerebrospinal fluid (CSF) inflammatory proteins have been reported in Alzheimer's disease (AD), yet whether they reflect peripheral immune cell infiltration or central nervous system (CNS)\u2013intrinsic pathological processes remains unclear. We tested whether AD exhibits a distinct CSF protein signature and how it relates to CSF immune cell composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We conducted a cross\u2010sectional study of 64 participants: 22 with biomarker\u2010confirmed AD (bioAD), 22 non\u2010AD biomarker\u2010negative cognitive controls (NAD\u2010CC), and 20 other neurological disease controls (OND). CSF proteins were quantified using the Olink Target 96 Inflammation panel, and immune cell populations were characterized by multiparameter spectral flow cytometry. Cell\u2013protein associations were assessed using hierarchical generalized linear models adjusted for age and sex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      BioAD showed widespread inflammatory and trophic protein elevation versus NAD\u2010CC, with 21 proteins significantly increased (false discovery rate [FDR]\n                      <jats:italic>q<\/jats:italic>\n                      &lt; 0.05), whereas NAD\u2010CC was largely indistinguishable from OND. MMP\u201010 showed the largest effect (geometric mean ratio [GMR] = 2.10, 95% confidence interval [CI]: 1.53\u20132.88,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). CSF immune cell populations did not differ significantly between groups; only discrete T\u2010cell alterations were detected: reduced regulatory T cells in bioAD relative to NAD\u2010CC (odds ratio [OR] = 0.69, 95% CI: 0.54\u20130.88,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.023), but not relative to OND and minor memory subset shifts. CD8+ effector memory T cells and TNFSF14 showed the only detected AD\u2010specific association: in bioAD, a 10\u2010fold increase in CD8+ EM2 cells corresponded to 70% higher TNFSF14 (GMR = 1.70, 95% CI: 1.39\u20132.09,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>In this feasibility\u2010sized, cross\u2010sectional cohort, CSF inflammatory proteins in AD appeared dissociated from immune\u2010cell composition, potentially reflecting CNS\u2010intrinsic processes and\/or altered CSF barrier dynamics. The identified signature, including MMP\u201010, is hypothesis\u2010generating and may complement conventional biomarkers for diagnosis and treatment monitoring, pending longitudinal validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70321","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:05:08Z","timestamp":1790226308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebrospinal fluid protein elevations in Alzheimer's disease are dissociated from immune cell composition"],"prefix":"10.1002","volume":"12","author":[{"given":"Sina","family":"Zaic","sequence":"first","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health, Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; 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