title: Increased CSF levels of phosphorylated neurofilament heavy protein following bout in amateur boxers.
abstract: BACKGROUND
  Diagnosis of mild TBI is hampered by the lack of imaging or biochemical measurements for identifying or quantifying mild TBI in a clinical setting. We have previously shown increased biomarker levels of protein reflecting axonal (neurofilament light protein and tau) and glial (GFAP and S-100B) damage in cerebrospinal fluid (CSF) after a boxing bout. The aims of this study were to find other biomarkers of mild TBI, which may help clinicians diagnose and monitor mild TBI, and to calculate the role of APOE ε4 allele genotype which has been associated with poor outcome after TBI.
  
  
  METHODS
  Thirty amateur boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in a prospective cohort study. CSF and blood were collected at one occasion between 1 and 6 days after a bout, and after a rest period for at least 14 days (follow up). The controls were tested once. CSF levels of neurofilament heavy (pNFH), amyloid precursor proteins (sAPPα and sAPPβ), ApoE and ApoA1 were analyzed. In blood, plasma levels of Aβ42 and ApoE genotype were analyzed.
  
  
  RESULTS
  CSF levels of pNFH were significantly increased between 1 and 6 days after boxing as compared with controls (p<0.001). The concentrations decreased at follow up but were still significantly increased compared to controls (p = 0.018). CSF pNFH concentrations correlated with NFL (r =  0.57 after bout and 0.64 at follow up, p<0.001). No significant change was found in the other biomarkers, as compared to controls. Boxers carrying the APOE ε4 allele had similar biomarker concentrations as non-carriers.
  
  
  CONCLUSIONS
  Subconcussive repetitive trauma in amateur boxing causes a mild TBI that may be diagnosed by CSF analysis of pNFH, even without unconsciousness or concussion symptoms. Possession of the APOE ε4 allele was not found to influence biomarker levels after acute TBI.
authors.affiliation: Department of Orthopaedics, Sahlgrenska University Hospital, Gothenburg, Sweden ; Institution for Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sanna
authors.initials: S
authors.lastname: Neselius
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Jan
authors.initials: J
authors.lastname: Marcusson
authors.forename: Helena
authors.initials: H
authors.lastname: Brisby
mesh_terms: D000483:Alleles; D016229:Amyloid beta-Peptides / Q000097:blood; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid / Q000235:genetics; D016632:Apolipoprotein A-I / Q000134:cerebrospinal fluid / Q000235:genetics; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001914:Boxing / Q000293:injuries*; D001930:Brain Injuries / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D011446:Prospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C505693:APOA1 protein, human; C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D015415:Biomarkers; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C051774:neurofilament protein H