{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T11:57:00Z","timestamp":1794571020373,"version":"4.9.1"},"posted":{"date-parts":[[2025,7,21]]},"group-title":"Neurology","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Brain-derived tau (BD-tau) is a promising blood-based biomarker for neurodegeneration\/brain injury in neurodegenerative and acute neurological disorders. However, widespread use is hampered by lack of commercial assays.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using the Simoa\u00ae HD-X analyzer, we evaluated the first commercial research-use only BD-tau Advantage PLUS assay\u2019s robustness, precision, dilution linearity, spike recovery, specificity, and limits of detection. Matrix effect was examined by comparing BD-tau levels in n=48 plasma\/serum and n=20 plasma\/CSF sample pairs. Clinical performance was examined in a traumatic brain injury (TBI) cohort.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty repeated measurements of three plasma samples gave intra- and inter-plate CVs \u22647.24%. A median drift of 8.00% (decrease) was observed from the start to the end of a full plate run. Analytically, BD-tau concentrations decreased linearly up to 16-fold dilution, spike recovery was 86-96%, and signals were highly specific to the CNS-abundant tau441 but not the peripherally-enriched \u201cbig-tau\u201d isoform. Moreover, signals were stable for up to four freeze\/thaw cycles. Furthermore, significant correlations were observed in the plasma\/serum (r=0.8392; p&lt;0.0001) and plasma\/CSF (r=0.6150; p=0.0039) pairs. Finally, plasma BD-tau was elevated in severe-acute TBI vs. chronic-mixed TBI and unaffected controls (p&lt;0.0001; AUC=0.9986, and p&lt;0.0001; AUC=1.000, respectively). In severe-acute TBI patients, plasma BD-tau was correlated with plasma p-tau217 (r=0.5761, p=0.0005), NfL (r=0.8910, p=0.0001), and GFAP (r=0.5424, p=0.0011). CSF BD-tau and CSF p-tau217 were strongly correlated (r=0.9667, p=0.0002).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>BD-tau Advantage PLUS produces robust brain-derived tau-specific readings that demonstrate utility in detecting severe-acute TBI.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.07.21.25331193","type":"posted-content","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T03:05:11Z","timestamp":1753153511000},"source":"Crossref","is-referenced-by-count":2,"title":["Plasma brain-derived tau: analytical and clinical validation of the first commercial immunoassay"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6953-075X","authenticated-orcid":false,"given":"Michel N.","family":"Nafash","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Svirsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia K.","family":"Kofler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann D.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7444-2851","authenticated-orcid":false,"given":"David O.","family":"Okonkwo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar L.","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ava M.","family":"Puccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-4358","authenticated-orcid":false,"given":"Thomas K.","family":"Karikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100904101168000_2025.07.21.25331193v2.1","doi-asserted-by":"crossref","unstructured":"Lle\u00f3, A . Biomarkers in neurological disorders: a fast-growing market. Brain Commun 3, fcab086 (2021).","DOI":"10.1093\/braincomms\/fcab086"},{"key":"2025100904101168000_2025.07.21.25331193v2.2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1067\/mcp.2001.113989","article-title":"Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework","volume":"69","year":"2001","journal-title":"Clinical Pharmacology & Therapeutics"},{"key":"2025100904101168000_2025.07.21.25331193v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.232"},{"key":"2025100904101168000_2025.07.21.25331193v2.4","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-32-9358-8_29"},{"key":"2025100904101168000_2025.07.21.25331193v2.5","doi-asserted-by":"publisher","DOI":"10.31887\/dcns.2004.6.4\/hhampel"},{"key":"2025100904101168000_2025.07.21.25331193v2.6","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac407"},{"key":"2025100904101168000_2025.07.21.25331193v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/J.CCA.2022.03.018"},{"key":"2025100904101168000_2025.07.21.25331193v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.4"},{"key":"2025100904101168000_2025.07.21.25331193v2.9","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/alz.13518","article-title":"Biological variation estimates of Alzheimer\u2019s disease plasma biomarkers in healthy individuals","volume":"20","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2025100904101168000_2025.07.21.25331193v2.10","doi-asserted-by":"crossref","unstructured":"Noda, K. , Lim, Y. , Goto, R. , Sengoku, S. & Kodama, K . Cost-effectiveness comparison between blood biomarkers and conventional tests in Alzheimer\u2019s disease diagnosis. Drug Discovery Today 29, 103911 (2024).","DOI":"10.1016\/j.drudis.2024.103911"},{"key":"2025100904101168000_2025.07.21.25331193v2.11","doi-asserted-by":"crossref","first-page":"8132","DOI":"10.3390\/ijms25158132","article-title":"Clinical Application of Blood Biomarkers in Neurodegenerative Diseases\u2014Present and Future Perspectives","volume":"25","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2025100904101168000_2025.07.21.25331193v2.12","doi-asserted-by":"crossref","unstructured":"Hardy-Sosa, A. et al. Diagnostic Accuracy of Blood-Based Biomarker Panels: A Systematic Review. Front Aging Neurosci 14, 683689 (2022).","DOI":"10.3389\/fnagi.2022.683689"},{"key":"2025100904101168000_2025.07.21.25331193v2.13","doi-asserted-by":"crossref","unstructured":"Shi, M. , Chu, F. , Zhu, F. & Zhu, J . Peripheral blood amyloid-\u03b2 involved in the pathogenesis of Alzheimer\u2019s disease via impacting on peripheral innate immune cells. Journal of Neuroinflammation 21, 5 (2024).","DOI":"10.1186\/s12974-023-03003-5"},{"key":"2025100904101168000_2025.07.21.25331193v2.14","doi-asserted-by":"crossref","unstructured":"Xu, B. et al. Peripheral proteinopathy in neurodegenerative diseases. 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