Brain-derived tau for monitoring brain injury in acute ischemic stroke

A specific and accurate blood test for acute brain injury could help monitor infarct growth in ischemic stroke and serve as a surrogate end point in clinical trials. Using a single-molecule detection assay, we assessed plasma brain-derived tau (BD-tau), a marker selectively quantifying tau protein from the central nervous system, in a prospective cohort of 502 patients with acute ischemic stroke with serial blood sampling from admission to day 7. Higher BD-tau concentrations at admission were associated with more extensive early brain injury on computed tomography and predicted larger final infarct volumes. BD-tau increases from admission to day 2 were related to infarct growth. BD-tau concentrations rose until day 7 and were higher in patients with secondary events, including recurrent stroke. After thrombectomy, the rise of BD-tau was smaller in patients with complete versus incomplete recanalization. BD-tau outperformed other blood markers and imaging metrics in predicting 90-day functional outcome across infarct size strata and time points. In an independent multicenter prospective cohort (<i>N</i> = 519), BD-tau showed higher performance than magnetic resonance imaging-derived final infarct volume in predicting functional outcomes at 3, 12, and 36 months. In the biomarker substudy of a phase 3 trial assessing nerinetide in patients with ischemic stroke (<i>N</i> = 193), BD-tau showed predictive performance comparable to the other cohorts, mediated the relationship between recanalization and functional outcome, and showed a 49% smaller increase in the nerinetide group versus placebo. Overall, plasma BD-tau tracked ischemic brain injury over time, outperformed other biomarkers in predicting functional outcomes, and identified possible treatment responses.

Authors

Institutions

Publication Details

Journal
Science Translational Medicine
Published
2026-01-14
DOI
https://doi.org/10.1126/scitranslmed.adz1280
Citations
1
Primary Topic
Acute Ischemic Stroke Management
Type
article
Field-Weighted Citation Impact
31.52
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Brain-derived tau for monitoring brain injury in acute ischemic stroke

Maria Kaffe, Julia Zeller, Gregor Bauer, Lilian Kriemler et al.
1 citations
Science Translational Medicine
Acute Ischemic Stroke Management
31.52
article

Brain-derived tau for monitoring brain injury in acute ischemic stroke

Maria Kaffe, Julia Zeller, Gregor Bauer, Lilian Kriemler, Franziska Müller, Dr Akshay Deepak, Carol E. Kenney, Robert Forbrig, Aditya Bharatha, Pia Kalmbach, Simon Schieber, Lukas Diebold, Anna-Lena Schwake, Axel C. Rohr, Harald Prüß, Stys Peter, Zul Kaderali, Alonso Alvarado Bolaños, DEMDAS Study Group, Michael Tymianski, Ozan Eren, William Guest, Lars Behrens, Pia S. Sperber, Nikolaos Ntoulias, Mirco Gindullis, Hani Ridwan, Gabriel BARBU, Stefanie Deuster, Alex Brehm, Lutz Schnabel, Christiane Katia Huber, Gökce Hatipoglu Majernik, Norma Krümmer, Renarebecca Sagayanathan, Thomas Liebig, Lars Johan Tveit, Stergios Tsitos, Anne Berberich, Andrea Stockero, Raymond C.S. Seet, Konstantinos A. Dimitriadis, Peter Cidlinsky, Sarbjeet Singh, Endres Matthias, Matthias S. Klein, Sharanpal Mann, Andrew Micieli, Cornelia Löffler, Hui Shi Lim, Stephanie Reiter, Jan F. Scheitz, Alexander V. Khaw, Timothy Bunck, Susan E. Alcock, Suneet Mangat, Ankur Wadhwa, Thomas Günthner‐Lengsfeld, Sherry Hu, Lindsay Lambourn, Heike Ehlers, Alexander März, Kolja Schürmann, Stefan Zülow, Tareq Meyer, Babawale Arabambi, Christian Brem, Jesper Sømark, M. Pham, Fabian Essig, Fabio Settecase, A Berlis, J. Gauri Shankar, C. Chahli, Marios K. Georgakis, Jörn Feick, Arndt Schievelkamp, Nils Lehnen, Thorsten Sichtermann, James McEachern, Karin Waegemann, Victor Schulze-Zachau, Karina Villaluna, Johannes Rückel, Jan Minkenberg, Alexandra Muccilli, Stephan Hause, Surbhi Chaturvedi, Rong Fang, Hanna Zimmermann, Philipp Vermehren, Mahtab Zamani, Thomas Liman, Dominik Lehrieder, Matthew Boyko, Johannes Wischmann, Johnathon Gorman, Paul Reidler, Marcus Blaum, Mona Skjelland, Johannes Frenger, Naomi Vlegels, Jule Filler, Fadi Al-Tinawi, Supriya S. Save, Alexander Marco Kollikowski, Christoph Vollmuth, Wolfram Schwindt, Alyson Plecash, Esseddeeg Ghrooda, M Dichgans, Ruchir A. Shah, Matthias N. Ungerer, João Pinho, Philip A. Barber, Steven Peters, Marius L. Vogt, Mark I. Boulos, Terje Nome, Kevin Lian, Thor Håkon Skattør, Yeyao Joe Yu, Sandra Hein, Anish Kapadia, Corinna Volpers, Janina Keilitz, Elisabeth Beyrle, D. Klunk, Anna Kufner Ibaroule, Prof. Dr. Mathias Bähr, Nicoló Luca Knuth, Linjie Zhang, Marco Marangoni, Shao Jin Ong, Cunli Yang, Meike Becker, Stephen James Ryan, Julia Reinhardt, Christine Kindler, Gernot Reimann, Julia J. Hopyan, Kamal Adeyemi, Mayank Goyal, Dawn-Lee McLaughlin, Atif Zafar, Christine Vogl, Mel Boulton, Mira Katan, Johannes Schiefer, Michael Görtler, Katja Neumann, Andrea Jaeger, Nada Khalifeh, Lana Toussaint, R Voigt, Philip Teal, Alexandra Gómez Expósito, Hariz Halik, Maksim Son, Tatjana Wittenberg, P Lohse, Kayla D. Sage, Lauren Mai, Anita Florendo Cumbermack, Shashank Bhoothanakudige Nagendra, Carolin Beuker, Inga Zerr, Anna Dewenter, Marco Duering, Charlotte Förster, Dimah Hasan, Sven Poli, Tony Stöcker, Benjamin Y. Q. Tan, Eric E. Smith, Gabor C Petzold, Vijay Kumar Sharma, Nicolai Franzmeier, Maria Richter, Christian Hagemann, Albrecht Bormann, Andrea Reiland, Brian Enriquez, Conny Sternitzky, Simerpreet Bal, Will Kingston, Michael Mayich, Salman Mansoor, Jyoti Patil, Simon Nagel, Maria Paulina Tieck Fernandez, Christian Gronemann, Michelle Damaskinos, Jennifer Sartor-Pfeiffer, Anil Gopinathan, Arno Reich, Joshua Mbroh, Tess Fitzpatrick, Beata Kozak, Zhang Ka, Joshua Bernick, Christoph Maurer, Julia Hopyan, Sebastian Fridman, Khouloud Poli, Mar Lloret, Christine Leypold, Leonard L. L. Yeo, Raed Joundi, Christine Hawkes, Nina Cryns, Ramy Abdelnaby, Katie Lin, Oliver Speck, Lena Mocza, Astrid Hauck, Joshua Y. P. Yeo, Michael Wagner, Lars Kellert, Gary Redekop, Marie Suttmann, Nazuk Nijjar, Johannes Tünnerhoff, Irem Mirzen, Caroline Herbst, Miguel Ángel Araque Caballero, Louisa Antonella Lehner, Gary Klein, Frank Wollenweber, Ryan Muir, Chin How Keat, Vivian Fu, Kerstin Burg, Aravind Ganesh, Julius N. Meißner, Melissa Mühling, Colleen B. Murphy, Margaret Moores, Beili Huang, Ansar Roy, Jennifer L. Mandzia, Suresh Subramanian, Maria Bres Bullrich, Diane Kim, Jintao Chen, Dilara Moumin, Chrysi Bogiatzi, Carson Ma, Johnathan B. Gorman, Vanessa Norouzi, Cha-Ney Kim, Samuel Yip, David Thomas Fischer, Megan Ng Bi Jia, Shivangi Pandya, Mohammed A. Almekhlafi, ESCAPE-NEXT biomarker substudy investigators‡, Anett Riedel-Stoll, Simon Grümme, Tolga Dittrich, Bjørn Tennøe, Carsten Schmeel, Peter Bartenstein, Simon Weiner, Richard Chan, Benno Ikenberg, Sonja Ruschitzka, Shelagh B. Coutts, Oliver Matz, Jörg B. Schulz, Idris Fatakdawala, Amanda X. Y. Chin, Miriam Heyse, Genoveva MacLean, Nishita Singh, Matthias Schmitz, Ng Jin Keat Sheldon, Peter Sporns, Michael Goertler, Peter Hermann, Christopher Y. K. Chua, Gian Marco de Marchis, Amro Lahlouh, Sabine Nuhn, Andrew M. Demchuk, Valentina Perosa, Oscar R. Benavente, Charlotte S. Weyland, Ming Yin Dominic Tse, Katharina Walter, Esther D’Andrade, Teoh Hock Luen, Amber Rear, May Alhamid, Hatyna Ferens, Leodante Da Costa, Franziska Dorn, Peter Dechent, Manas Sharma, Jose Danilo Bengzon Diestro, Maximillian Bellut, Lee Lau, Imaine Ben Jemaa, Bernard P. L. Chan, Laura Parsons, Inga-Tatiana Hagström, Wenzel Glanz, Bijoy K. Menon, Perdita Beck, Princess King-Azote, Alisia Southwell, Silvia Schönenberger, Susanne Bonekamp, Teye Umanah, Apolline L. Vix, Srees Durga, Ashish Kumar, Beth Beauchamp, Silvana Vierbeck, Gabriele Neureither, Laura Dobisch, Kathleen Bernkopf, Joseph Silvagio, Vitor Pereira, Mahsa Sadeghi, Julia Nordsiek, Jing Mingxue, Luciano A. Sposato, Alexander H. Nave, Audrey Bhairo, Felix J. Bode, Anna Kopczak, Kimia Ghavami, Omid Nikoubashman, Peter Ringleb, Stephen C. Van Gaal, Sandra Becker, Ahn Ngugen, Ole Johannsmann, Ng Shiyang, Philippe Couillard, Kristine Blackham, Sebastian Stösser, Silke Wunderlich, Courtney Casserly, Jan Purrucker, Konstantin A. Steiner, Judy Yip, Martina Langguth, Niklas Beckonert, Marco Düring, Charles Haw, Anne Henn, Silke Breunig, Aderaldo Costa-Alves, Christian Hametner, Karla J. Ryckborst, Katrina Hannah D. Ignacio, Anurag Tirvedi, Najla Popel, Christian H. Nolte, Christine Tunkl, Jonathan D Smith, David J. Gladstone, Hanna Mellage, Myint May Zin, Thomas R. Marotta, Emrah Duezel, Thalia S. Field, Christian-Paul Stracke, Manohari A. Mohamad, Michael Gunderson, Marios-Nikos Psychogios, Jiechu Chen, Andrea Gerecke, Daniela Geier, Ignaz Arnulf Steiger, Pakar Kayenat, Marios N Psychogios, Stefan Goebel, Yanyan Xiong, Claudia Kruse, Sachin K. Pandey, Sibu Mundiyanapurath, Anja Schaller, Martin Wiesmann, Nicole Ng Wan Ying, Holger Poppert, Manraj K. S. Heran, Margit Millan, Ioannis Tsogka, Amy X. Y. Yu, Clare Angeli Enriquez, Inga Holter, Birk Denise, Sara Schmidt, Fong Joon Sung, Steffen Tiedt, Abdullah Alfajri, Claudia T. M. Koh, Michael D. Hill, Anna Liu, Elona Mecaj, Keith Sivakumar, Ann Dowbenka, Lily W. Zhou, Lucia Kerti, Lily Wong, Goh Yi Hui
article en
1 citations

Abstract

A specific and accurate blood test for acute brain injury could help monitor infarct growth in ischemic stroke and serve as a surrogate end point in clinical trials. Using a single-molecule detection assay, we assessed plasma brain-derived tau (BD-tau), a marker selectively quantifying tau protein from the central nervous system, in a prospective cohort of 502 patients with acute ischemic stroke with serial blood sampling from admission to day 7. Higher BD-tau concentrations at admission were associated with more extensive early brain injury on computed tomography and predicted larger final infarct volumes. BD-tau increases from admission to day 2 were related to infarct growth. BD-tau concentrations rose until day 7 and were higher in patients with secondary events, including recurrent stroke. After thrombectomy, the rise of BD-tau was smaller in patients with complete versus incomplete recanalization. BD-tau outperformed other blood markers and imaging metrics in predicting 90-day functional outcome across infarct size strata and time points. In an independent multicenter prospective cohort (<i>N</i> = 519), BD-tau showed higher performance than magnetic resonance imaging-derived final infarct volume in predicting functional outcomes at 3, 12, and 36 months. In the biomarker substudy of a phase 3 trial assessing nerinetide in patients with ischemic stroke (<i>N</i> = 193), BD-tau showed predictive performance comparable to the other cohorts, mediated the relationship between recanalization and functional outcome, and showed a 49% smaller increase in the nerinetide group versus placebo. Overall, plasma BD-tau tracked ischemic brain injury over time, outperformed other biomarkers in predicting functional outcomes, and identified possible treatment responses.

Science Translational MedicineVol. 18(832)
Western University (CA), Oslo University Hospital (NO), St. Michael's Hospital (CA), Sunnybrook Health Science Centre (CA), University of British Columbia (CA), National University of Singapore (SG), University of Calgary (CA), University of Basel (CH), Heidelberg University (DE), University Hospital Bonn (DE), London Health Sciences Centre (CA), German Center for Neurodegenerative Diseases (DE), University Hospital Augsburg (DE), University Hospital Heidelberg (DE), University Hospital of Basel (CH), TUM Klinikum (DE), LMU Klinikum (DE), Humboldt-Universität zu Berlin (DE), Klinikum Altenburger Land (DE), University Hospital Münster (DE), University Hospital Schleswig-Holstein (DE), Munich Cluster for Systems Neurology (DE), NoNO (Canada) (CA), Universitätsmedizin Göttingen (DE), University Children's Hospital Tübingen (DE), Universitätsklinikum Würzburg (DE), Technical University of Applied Sciences Lübeck (DE), Klinikum Dortmund (DE), German Centre for Cardiovascular Research (DE), St Michael's Hospital (GB), German Society for Thoracic and Cardiovascular Surgery (DE), University of Manitoba (CA), Technische Universität Dresden (DE), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE), University of Gothenburg (SE), RWTH Aachen University (DE), University of Lübeck (DE), Otto-von-Guericke-Universität Magdeburg (DE)
Good health and well-being
Openalex Percentile: Top 2%
Acute Ischemic Stroke Management
31.52
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.