Naomi Vlegels, Naomi Vlegels, Nicoló Luca Knuth, Nicoló L. Knuth, Konstantin A. Steiner, Linjie Zhang, Apolline L. Vix, Dilara Moumin, Irem Mirzen, Nada Khalifeh, Charlotte Forster, Benno Gesierich, Franziska Müller, P Lohse, Jule Filler, Rong Fang, Matthias S. Klein, Konstantinos Dimitriadis, Nicolai Franzmeier, Thomas Liebig, Matthias Endres, Michael Goertler, Gabor C. Petzold, Silke Wunderlich, Inga Zerr, Thalia S. Field, M. Pham, Richard H. Swartz, Sven Poli, Jörg Berrouschot, Atif Zafar, Hauke Schneider, Jai J. Shankar, Anne Hege Aamodt, Jens Minnerup, Jennifer L. Mandzia, Gernot Reimann, Marios-Nikos Psychogios, Sibu Mundiyanapurath, Arno Reich, Leonard L. L. Yeo, Marco Duering, Paul Reidler, DEMDAS Study Group, ESCAPE-NEXT biomarker substudy investigators‡, Mayank Goyal, Michael Tymianski, Michael D. Hill, Martin Dichgans, Steffen Tiedt, Matthias Endres, Emrah Duezel, Lucia Kerti, Katja Neumann, Julius N. Meißner, Thomas Liman, Christian H. Nolte, Tatjana Wittenberg, Jan F. Scheitz, Harald Prüß, Pia S. Sperber, Alexander H. Nave, Anna Kufner Ibaroule, Gabor Petzold, Felix Bode, Sebastian Stösser, Taraneh Ebrahimi, Julia Nordsiek, Julius N. Meißner, Niklas Beckonert, Christine Kindler, Inga Zerr, Peter Hermann, Matthias Schmitz, Stefan Goebel, Timothy Bunck, Julia Schütte-Schmidt, Sabine Nuhn, Corinna Volpers, Peter Dechent, Prof. Dr. Mathias Bähr, Michael Görtler, Wenzel Glanz, Valentina Perosa, Martin Dichgans, Frank Wollenweber, Marios Georgakis, Rong Fang, Daniel Janowitz, Karin Waegemann, Steffen Tiedt, Silke Wunderlich, Benno Ikenberg, Kathleen Bernkopf, Christiane Katia Huber, Holger Poppert, Marco Düring, Miguel Ángel Araque Caballero, Benno Gesierich, Anna Dewenter
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 ( N = 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 ( N = 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.