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@ARTICLE{Halbgebauer:285160,
      author       = {Halbgebauer, Rebecca and Gonzalez-Ortiz, Fernando and
                      Mayer, Benjamin and Berger, Claudius and Bergmann, Christian
                      and Rinderknecht, Helen and Barth, Eberhard and Wohlgemuth,
                      Lisa and Mannes, Marco and Otto, Markus and Tumani,
                      Hayrettin and Relja, Borna and Gebhard, Florian and
                      Huber-Lang, Markus and Zetterberg, Henrik and Halbgebauer,
                      Steffen and Blennow, Kaj},
      title        = {{B}lood-{B}ased {A}nalysis of {D}ifferent {T}au {V}ariants
                      in {P}atients {W}ith {M}ultiple {T}raumatic {I}njuries.},
      journal      = {JAMA network open},
      volume       = {9},
      number       = {2},
      issn         = {2574-3805},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {DZNE-2026-00182},
      pages        = {e2558573},
      year         = {2026},
      abstract     = {With blood-based phosphorylated tau biomarkers soon to be
                      used for diagnosis of Alzheimer disease, analyzing tau
                      levels in other conditions could enhance biomarker
                      interpretability. Moreover, mechanisms of tau release into
                      circulation remain unclear.To evaluate concentrations of
                      phosphorylated and nonphosphorylated tau variants in the
                      blood of patients with multiple traumatic injuries on days
                      0, 1, 5, and 10 and investigate biological processes driving
                      tau release.This multiple-trauma cohort (injury severity
                      score, ≥18) included 45 severely injured patients with (n
                      = 27) and without (n = 18) moderate-to-severe traumatic
                      brain injury on emergency computed tomographic imaging.
                      Controls consisted of 24 healthy volunteers. Participants
                      were recruited from December 1, 2013, to October 31, 2022.
                      Blood samples were analyzed for brain-derived tau (BD-tau),
                      total tau (t-tau), and phosphorylated tau 217 (p-tau217) and
                      231 (p-tau231) levels. Associations among tau
                      concentrations, clinical data, and outcome (eg, Glasgow Coma
                      Scale [GCS] score) were assessed. Data were analyzed from
                      March 1, 2023, to September 30, 2024.Serum BD-tau, t-tau,
                      p-tau217, and p-tau231 levels.A total of 214 serum samples
                      were analyzed. Median age of the 45 patients was 48 (IQR,
                      33-60) years (35 $[77.8\%]$ male); median age of the 24
                      controls, 43 (IQR, 28-50) years (16 $[66.7\%]$ male). Median
                      serum levels of tau variants were increased in patients with
                      multiple traumatic injuries at day 0 compared with controls
                      (t-tau: 43 [IQR, 21-95] vs 3 [IQR, 3-5] pg/mL; BD-tau: 78
                      [IQR, 30-343] vs 2 [IQR, 2-3] pg/mL; p-tau231: 61 [IQR,
                      21-79] vs 2 [IQR, 1-3] pg/mL; all, P < .001). Only median
                      BD-tau levels remained elevated until day 10 (day 1, 25
                      [IQR, 14-69] pg/mL; day 5, 9 [IQR, 4-15] pg/mL; day 10, 8
                      [IQR, 4-18] pg/mL). Median tau levels at admission were
                      higher in patients with lower GCS scores (BD-tau: 107 [ IQR,
                      59-838] vs 33 [IQR, 24-78] pg/mL [P = .01]; p-tau231: 76
                      [IQR, 36-114] vs 28 [IQR, 9-63] pg/mL [P = .02]). Elevated
                      median tau levels were also observed in patients with
                      hemorrhagic shock vs those without shock (eg, BD-tau on day
                      0: 113 [IQR, 78-378] vs 31 [IQR, 24-61] pg/mL; P = .002) and
                      in nonsurvivors vs survivors with uncomplicated courses (eg,
                      BD-tau on day 1: 92 [IQR, 22-527] vs 16 [IQR, 7-23] pg/mL; P
                      = .009).In this exploratory study among a cohort of patients
                      with multiple traumatic injuries, levels of tau variants
                      reflected both direct and indirect neurological injury, with
                      BD-tau showing the most persistent elevation in the acute
                      phase.},
      keywords     = {Humans / tau Proteins: blood / Male / Female / Adult /
                      Middle Aged / Biomarkers: blood / Brain Injuries, Traumatic:
                      blood / Phosphorylation / Cohort Studies / Case-Control
                      Studies / tau Proteins (NLM Chemicals) / Biomarkers (NLM
                      Chemicals) / MAPT protein, human (NLM Chemicals)},
      cin          = {Clinical Study Center (Ulm)},
      ddc          = {610},
      cid          = {I:(DE-2719)5000077},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41665901},
      doi          = {10.1001/jamanetworkopen.2025.58573},
      url          = {https://pub.dzne.de/record/285160},
}