TY - JOUR
T1 - Admission Levels of Total Tau and β-Amyloid Isoforms 1–40 and 1–42 in Predicting the Outcome of Mild Traumatic Brain Injury
AU - Hossain, Iftakher
AU - Mohammadian, Mehrbod
AU - Takala, Riikka S.K.
AU - Tenovuo, Olli
AU - Azurmendi Gil, Leire
AU - Frantzén, Janek
AU - van Gils, Mark
AU - Hutchinson, Peter J.
AU - Katila, Ari J.
AU - Maanpää, Henna Riikka
AU - Menon, David K.
AU - Newcombe, Virginia F.
AU - Tallus, Jussi
AU - Hrusovsky, Kevin
AU - Wilson, David H.
AU - Gill, Jessica
AU - Blennow, Kaj
AU - Sanchez, Jean Charles
AU - Zetterberg, Henrik
AU - Posti, Jussi P.
N1 - Funding Information:
Conflict of Interest: RT has received speakers fee from Abbott, Fresenius-Kabi, Orion and UCB, conference funding from Pfizer and Steripolar and is stockholder of Orion. DM reports collaborative research or consultancy agreements with GlaxoSmithKline Ltd; Ornim Medical; Shire Medical; Calico Inc; Pfizer Ltd; Pressura Ltd; Glide Pharma Ltd; NeuroTraumaSciences LLC; Lantasman AB. HZ has served at advisory boards for Roche Diagnostics, Wave, Samumed and CogRx, has participated in symposia sponsored by Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. KB has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. JP has received speaker’s fees from Orion corporation and Finnish Medical Association and a travel grant from Stryker Corporation.
Funding Information:
This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), Integra EANS Research Grant (IH), Orion Research Foundation sr (IH), University of Turku Graduate School funding (MM), Academy of Finland (#17379, JP), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland) (JP), Emil Aaltonen Foundation sr (JP), Finnish Brain Foundation sr (JP), Maire Taponen Foundation (JP), and NIHR Research Fellowship (PH). VN is funded by the Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship. HZ is a Wallenberg Academy Fellow and holds grants from the Swedish and European Research Councils. KB holds the Torsten Söderberg Professorship in Medicine, awarded by the Royal Swedish Academy of Sciences, and holds grants from the Swedish Research Council. The authors thank our research nurses Patricia Bertenyi and Satu Honkala for their valuable contribution to this study.
Publisher Copyright:
© Copyright © 2020 Hossain, Mohammadian, Takala, Tenovuo, Azurmendi Gil, Frantzén, van Gils, Hutchinson, Katila, Maanpää, Menon, Newcombe, Tallus, Hrusovsky, Wilson, Gill, Blennow, Sanchez, Zetterberg and Posti.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/13
Y1 - 2020/5/13
N2 - Background: The purpose of this study was to investigate if admission levels of total tau (T-tau) and β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42) could predict clinical outcome in patients with mild traumatic brain injury (mTBI). Methods: A total of 105 patients with mTBI [Glasgow Coma Scale (GCS) ≥ 13] recruited in Turku University Hospital, Turku, Finland were included in this study. Blood samples were drawn within 24 h of admission for analysis of plasma T-tau, Aβ40, and Aβ42. Patients were divided into computed tomography (CT)-positive and CT-negative groups. The outcome was assessed 6–12 months after the injury using the Extended Glasgow Outcome Scale (GOSE). Outcomes were defined as complete (GOSE 8) or incomplete (GOSE < 8) recovery. The Rivermead Post Concussion Symptoms Questionnaire (RPCSQ) was also used to assess mTBI-related symptoms. Predictive values of the biomarkers were analyzed independently, in panels and together with clinical parameters. Results: The admission levels of plasma T-tau, Aβ40, and Aβ42 were not significantly different between patients with complete and incomplete recovery. The levels of T-tau, Aβ40, and Aβ42 could poorly predict complete recovery, with areas under the receiver operating characteristic curve 0.56, 0.52, and 0.54, respectively. For the whole cohort, there was a significant negative correlation between the levels of T-tau and ordinal GOSE score (Spearman ρ = −0.231, p = 0.018). In a multivariate logistic regression model including age, GCS, duration of posttraumatic amnesia, Injury Severity Score (ISS), time from injury to sampling, and CT findings, none of the biomarkers could predict complete recovery independently or together with the other two biomarkers. Plasma levels of T-tau, Aβ40, and Aβ42 did not significantly differ between the outcome groups either within the CT-positive or CT-negative subgroups. Levels of Aβ40 and Aβ42 did not significantly correlate with outcome, but in the CT-positive subgroup, the levels of T-tau significantly correlated with ordinal GOSE score (Spearman ρ = −0.288, p = 0.035). The levels of T-tau, Aβ40, and Aβ42 were not correlated with the RPCSQ scores. Conclusions: The early levels of T-tau are correlated with the outcome in patients with mTBI, but none of the biomarkers either alone or in any combinations could predict complete recovery in patients with mTBI.
AB - Background: The purpose of this study was to investigate if admission levels of total tau (T-tau) and β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42) could predict clinical outcome in patients with mild traumatic brain injury (mTBI). Methods: A total of 105 patients with mTBI [Glasgow Coma Scale (GCS) ≥ 13] recruited in Turku University Hospital, Turku, Finland were included in this study. Blood samples were drawn within 24 h of admission for analysis of plasma T-tau, Aβ40, and Aβ42. Patients were divided into computed tomography (CT)-positive and CT-negative groups. The outcome was assessed 6–12 months after the injury using the Extended Glasgow Outcome Scale (GOSE). Outcomes were defined as complete (GOSE 8) or incomplete (GOSE < 8) recovery. The Rivermead Post Concussion Symptoms Questionnaire (RPCSQ) was also used to assess mTBI-related symptoms. Predictive values of the biomarkers were analyzed independently, in panels and together with clinical parameters. Results: The admission levels of plasma T-tau, Aβ40, and Aβ42 were not significantly different between patients with complete and incomplete recovery. The levels of T-tau, Aβ40, and Aβ42 could poorly predict complete recovery, with areas under the receiver operating characteristic curve 0.56, 0.52, and 0.54, respectively. For the whole cohort, there was a significant negative correlation between the levels of T-tau and ordinal GOSE score (Spearman ρ = −0.231, p = 0.018). In a multivariate logistic regression model including age, GCS, duration of posttraumatic amnesia, Injury Severity Score (ISS), time from injury to sampling, and CT findings, none of the biomarkers could predict complete recovery independently or together with the other two biomarkers. Plasma levels of T-tau, Aβ40, and Aβ42 did not significantly differ between the outcome groups either within the CT-positive or CT-negative subgroups. Levels of Aβ40 and Aβ42 did not significantly correlate with outcome, but in the CT-positive subgroup, the levels of T-tau significantly correlated with ordinal GOSE score (Spearman ρ = −0.288, p = 0.035). The levels of T-tau, Aβ40, and Aβ42 were not correlated with the RPCSQ scores. Conclusions: The early levels of T-tau are correlated with the outcome in patients with mTBI, but none of the biomarkers either alone or in any combinations could predict complete recovery in patients with mTBI.
KW - outcome
KW - total tau
KW - traumatic brain injury
KW - β-amyloid 1-40
KW - β-amyloid 1-42
UR - http://www.scopus.com/inward/record.url?scp=85085398081&partnerID=8YFLogxK
U2 - 10.3389/fneur.2020.00325
DO - 10.3389/fneur.2020.00325
M3 - Article
C2 - 32477238
AN - SCOPUS:85085398081
SN - 1664-2295
VL - 11
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 325
ER -