The evolution of infarcts varies widely among patients with acute ischemic stroke (IS) and influences treatment decisions. Neuroimaging is not applicable for frequent monitoring and there is no blood-based biomarker to track ongoing brain injury in acute IS. Here, we examined the utility of plasma brain-derived tau (BD-tau) as a biomarker for brain injury in acute IS. We conducted the prospective, observational Precision Medicine in Stroke [PROMISE] study with serial blood sampling upon hospital admission and at days 2, 3, and 7 in patients with acute IS and for comparison, in patients with stroke mimics (SM). We determined the temporal course of plasma BD-tau, its relation to infarct size and admission imaging-based metrics of brain injury, and its value to predict functional outcome. Upon admission (median time-from-onset, 4.4h), BD-tau levels in IS patients correlated with ASPECTS (ρ=-0.21, P<.0001) and were predictive of final infarct volume (ρ=0.26, P<.0001). In contrast to SM patients, BD-tau levels in IS patients increased from admission (median, 2.9 pg/ml [IQR, 1.8-4.8]) to day 2 (median time-from-onset, 22.7h; median BD-tau, 5.0 pg/ml [IQR, 2.6-10.3]; P<.0001). The rate of change of BD-tau from admission to day 2 was significantly associated with collateral supply (R2=0.10, P<.0001) and infarct progression (ρ=0.58, P<.0001). At day 2, BD-tau was predictive of final infarct volume (ρ=0.59, P<.0001) and showed superior value for predicting the 90-day mRS score compared with final infarct volume. In conclusion, in 502 patients with acute IS, plasma BD-tau was associated with imaging-based metrics of brain injury upon admission, increased within the first 24 hours in correlation with infarct progression, and at 24 hours was superior to final infarct volume in predicting 90-day functional outcome. Further research is needed to determine whether BD-tau assessments can inform decision-making in stroke care.

KB has served as a consultant and at advisory boards for Acumen, ALZPath, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. TL protors and consults for Stryker, phenox, Acandis, and has in the past received suport for travel and service related fees from Medtronic, Pfizer, Cerus Endovascular, Sequent, and Microvention. NV, NLK, MD, and ST report a patent on the use of BD-tau. No other disclosures were reported.

F.G.-O. was funded by the Anna Lisa and Brother Bjornssons Foundation and Emil och Maria Palms Foundation. S. T. was supported by grants from the Corona foundation (S199/10081/2020), the Leducq foundation (21CVD04), and the Friedrich-Baur-Stiftung (52/23). TKK was supported by grants P30 AG066468, RF1 AG052525-01A1, R01 AG053952-05, R37 AG023651-17, RF1 AG025516-12A1, R01 AG073267-02, R01 AG075336-01, R01 AG072641-02, and P01 AG025204-16 from the National Institutes of Health; the Swedish Research Council (Vetenskapradet; 2021-03244); the Alzheimers Association (AARF-21-850325); the Swedish Alzheimer Foundation (Alzheimerfonden); the Aina (Ann) Wallstroms and Mary-Ann Sjobloms stiftelsen; and the Emil och Wera Cornells stiftelsen. KB is supported by the Swedish Research Council (#2017-00915 and #2022-00732), Hjarnfonden, Sweden (#FO2017-0243 and #ALZ2022-0006), and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG-965240).

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