Serum neurofilament light protein predicts clinical outcome in traumatic brain injury.
Axonal white matter injury is believed to be a major determinant of adverse outcomes following traumatic brain injury (TBI). We hypothesized that measurement of neurofilament light protein (NF-L), a protein found in long white-matter axons, in blood samples, may serve as a suitable biomarker for neuronal damage in TBI patients. To test our hypotheses, we designed a study in two parts: i) we developed an immunoassay based on Single molecule array technology for quantification of NF-L in blood, and ii) in a proof-of-concept study, we tested our newly developed method on serial serum samples from severe TBI (sTBI) patients (n = 72) and controls (n = 35). We also compared the diagnostic and prognostic utility of NF-L with the established blood biomarker S100B. NF-L levels were markedly increased in sTBI patients compared with controls. NF-L at admission yielded an AUC of 0.99 to detect TBI versus controls (AUC 0.96 for S100B), and increased to 1.00 at day 12 (0.65 for S100B). Importantly, initial NF-L levels predicted poor 12-month clinical outcome. In contrast, S100B was not related to outcome. Taken together, our data suggests that measurement of serum NF-L may be useful to assess the severity of neuronal injury following sTBI.
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, SE-43180 Mölndal, Sweden.
Pashtun
P
Shahim
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, SE-43180 Mölndal, Sweden.
Magnus
M
Gren
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, SE-43180 Mölndal, Sweden.
Victor
V
Liman
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, SE-43180 Mölndal, Sweden.
Ulf
U
Andreasson
UmanDiagnostics, Umeå, Sweden.
Niklas
N
Norgren
Division of Medical Sciences, Department of Health Sciences, Luleå University of Technology, SE 971 87 Luleå, Sweden.
Yelverton
Y
Tegner
Clinical Memory Research Unit, Lund University, Malmö, Sweden.
Niklas
N
Mattsson
Department of NVS, Karolinska Institute, Center for Alzheimer Research, Stockholm, Sweden.
Niels
N
Andreasen
Department of Anaesthesiology and Intensive Care, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Martin
M
Öst
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, SE-43180 Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N1PJ, UK.
Henrik
H
Zetterberg
Department of Anaesthesiology and Intensive Care, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Bengt
B
Nellgård
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, SE-43180 Mölndal, Sweden.
Kaj
K
Blennow
D000328:Adult; D019540:Area Under Curve; D001369:Axons / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D000070642:Brain Injuries, Traumatic / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood*; D009474:Neurons / Q000473:pathology*; D011379:Prognosis; D015203:Reproducibility of Results; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C044882:neurofilament protein L