{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T04:26:29Z","timestamp":1793593589574,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["STI2030\u2010Major Projects \u2013 2021ZD0201802"],"award-info":[{"award-number":["STI2030\u2010Major Projects \u2013 2021ZD0201802"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U20A20354"],"award-info":[{"award-number":["U20A20354"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U19 AG024904"],"award-info":[{"award-number":["U19 AG024904"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>ATN\u2010stratified cerebrospinal fluid (CSF) proteomic signals may partly reflect classifier tau immunoassays; reproducible non\u2010tau signals and CSF\u2013plasma differences remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We profiled CSF from 60 A\n                      <jats:sup>+<\/jats:sup>\n                      Beijing patients with Alzheimer's disease (AD) and 875 A\n                      <jats:sup>+<\/jats:sup>\n                      Alzheimer's Disease Neuroimaging Initiative (ADNI) participants using the NULISAseq CNS Disease Panel. Differential expression was assessed using a false discovery rate (FDR)\u00a0&lt;\u00a00.05 and |log\n                      <jats:sub>2<\/jats:sub>\n                      FC|\u22650.5 across three ATN contrasts. We also analyzed ADNI plasma, protein\u2013cognition correlations, tau\u2010adjusted associations, and nested models comparing non\u2010tau proteins with tau biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Eight CSF proteins met the cross\u2010cohort criterion within at least one matched contrast: pTau\u2010217, pTau\u2010181, pTau\u2010231, MAPT, SMOC1, MDH1, VSNL1, and FABP3. NULISA tau correlated with INNOTEST (\u03c1\u00a0=\u00a00.75\u20130.85) and Elecsys (\u03c1\u00a0=\u00a00.65\u20130.68). T and N classifications agreed for 94.6% of ADNI participants (\u03ba\u00a0=\u00a00.880); after adjustment for CSF pTau\u2010217, all 12 associations involving the four non\u2010tau proteins retained their direction and FDR support. In CSF, Elecsys p\u2010tau181 and NULISA tau\u2010family analytes had the strongest cognitive correlations (mean |\u03c1|\u00a0=\u00a00.35 and 0.29\u20130.34, respectively), followed by FABP3 (0.24). Adding the four\u2010protein block after tau increased cross\u2010validated\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      across all three cross\u2010sectional outcomes in models without diagnosis (+0.0101 to +0.0265), most clearly for the Alzheimer's Disease Assessment Scale\u2013Cognitive Subscale, 13\u2010item version (ADAS\u2010Cog13); diagnosis\u2010conditioned models showed no stable increment beyond tau and clinical characteristics. In plasma, pTau\u2010217 was the only analyte that met both thresholds in all three contrasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      CSF NULISAseq identified a reproducible tau\u2010associated signature across A\n                      <jats:sup>+<\/jats:sup>\n                      cohorts that extended beyond the tau family. The four non\u2010tau proteins extend the molecular profile associated with tau\u2010defined disease state and merit further evaluation for biological stratification in independent cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71915","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:17:40Z","timestamp":1791800260000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross\u2010cohort NULISAseq identifies tau\u2010anchored CSF and plasma\u2010specific signatures across the amyloid\u2010positive Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Lan","family":"Ding","sequence":"first","affiliation":[{"name":"Chinese Institutes for Medical Research, Beijing (CIMR) Capital Medical University  Beijing P. R. China"},{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Liu","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Liang","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Xie","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Sheng","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing P. R. 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China"},{"name":"Center of Alzheimer's Disease Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders Capital Medical University  Beijing P. R. 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