Admission Levels of Total Tau and β-Amyloid Isoforms 1–40 and 1–42 in Predicting the Outcome of Mild Traumatic Brain Injury

Iftakher Hossain; Mehrbod Mohammadian; Riikka S.K. Takala; Olli Tenovuo; Leire Azurmendi Gil; Janek Frantzén; Mark van Gils; Peter J. Hutchinson; Ari J. Katila; Henna Riikka Maanpää; David K. Menon; Virginia F. Newcombe; Jussi Tallus; Kevin Hrusovsky; David H. Wilson; Jessica Gill; Kaj Blennow; Jean Charles Sanchez; Henrik Zetterberg; Jussi P. Posti

doi:10.3389/fneur.2020.00325

Admission Levels of Total Tau and β-Amyloid Isoforms 1–40 and 1–42 in Predicting the Outcome of Mild Traumatic Brain Injury

Iftakher Hossain, Mehrbod Mohammadian, Riikka S.K. Takala, Olli Tenovuo, Leire Azurmendi Gil, Janek Frantzén, Mark van Gils, Peter J. Hutchinson, Ari J. Katila, Henna Riikka Maanpää, David K. Menon, Virginia F. Newcombe, Jussi Tallus, Kevin Hrusovsky, David H. Wilson, Jessica Gill, Kaj Blennow, Jean Charles Sanchez, Henrik Zetterberg, Jussi P. Posti^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

13 Citations (Scopus)

37 Downloads (Pure)

Abstract

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.

Original language	English
Article number	325
Journal	Frontiers in Neurology
Volume	11
DOIs	https://doi.org/10.3389/fneur.2020.00325
Publication status	Published - 13 May 2020
MoE publication type	A1 Journal article-refereed

Funding

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. JP has received speaker’s fees from Orion corporation and Finnish Medical Association and a travel grant from Stryker Corporation.

Keywords

outcome
total tau
traumatic brain injury
β-amyloid 1-40
β-amyloid 1-42

Access to Document

10.3389/fneur.2020.00325Licence: CC BY

fneur.2020.00325Final published version, 576 KBLicence: CC BY

Cite this

Hossain, I., Mohammadian, M., Takala, R. S. K., Tenovuo, O., Azurmendi Gil, L., Frantzén, J., van Gils, M., Hutchinson, P. J., Katila, A. J., Maanpää, H. R., Menon, D. K., Newcombe, V. F., Tallus, J., Hrusovsky, K., Wilson, D. H., Gill, J., Blennow, K., Sanchez, J. C., Zetterberg, H., & Posti, J. P. (2020). Admission Levels of Total Tau and β-Amyloid Isoforms 1–40 and 1–42 in Predicting the Outcome of Mild Traumatic Brain Injury. Frontiers in Neurology, 11, Article 325. https://doi.org/10.3389/fneur.2020.00325

@article{ab0f9ecb3b2143d19adbc78f2ba33064,

title = "Admission Levels of Total Tau and β-Amyloid Isoforms 1–40 and 1–42 in Predicting the Outcome of Mild Traumatic Brain Injury",

abstract = "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.",

keywords = "outcome, total tau, traumatic brain injury, β-amyloid 1-40, β-amyloid 1-42",

author = "Iftakher Hossain and Mehrbod Mohammadian and Takala, {Riikka S.K.} and Olli Tenovuo and {Azurmendi Gil}, Leire and Janek Frantz{\'e}n and {van Gils}, Mark and Hutchinson, {Peter J.} and Katila, {Ari J.} and Maanp{\"a}{\"a}, {Henna Riikka} and Menon, {David K.} and Newcombe, {Virginia F.} and Jussi Tallus and Kevin Hrusovsky and Wilson, {David H.} and Jessica Gill and Kaj Blennow and Sanchez, {Jean Charles} and Henrik Zetterberg and Posti, {Jussi P.}",

year = "2020",

month = may,

day = "13",

doi = "10.3389/fneur.2020.00325",

language = "English",

volume = "11",

journal = "Frontiers in Neurology",

issn = "1664-2295",

publisher = "Frontiers Media",

}

Hossain, I, Mohammadian, M, Takala, RSK, Tenovuo, O, Azurmendi Gil, L, Frantzén, J, van Gils, M, Hutchinson, PJ, Katila, AJ, Maanpää, HR, Menon, DK, Newcombe, VF, Tallus, J, Hrusovsky, K, Wilson, DH, Gill, J, Blennow, K, Sanchez, JC, Zetterberg, H & Posti, JP 2020, 'Admission Levels of Total Tau and β-Amyloid Isoforms 1–40 and 1–42 in Predicting the Outcome of Mild Traumatic Brain Injury', Frontiers in Neurology, vol. 11, 325. https://doi.org/10.3389/fneur.2020.00325

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.

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 -

Admission Levels of Total Tau and β-Amyloid Isoforms 1–40 and 1–42 in Predicting the Outcome of Mild Traumatic Brain Injury

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this