title: Astroglial activation and altered amyloid metabolism in human repetitive concussion.
abstract: OBJECTIVE
  To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment.
  
  
  METHODS
  A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Aβ38, Aβ40, Aβ42, sAPPα, and sAPPβ), and BBB function (CSF:serum albumin ratio).
  
  
  RESULTS
  Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS >1 year. Athletes with PCS >1 year had higher RPQ scores and number of concussions than athletes with PCS <1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS >1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of Aβ40 and Aβ42 than controls. The CSF:serum albumin ratio was unaltered.
  
  
  CONCLUSIONS
  This study suggests that PCS may be associated with biomarker evidence of astroglial activation and β-amyloid (Aβ) dysmetabolism in the brain. There was no clear evidence of Aβ deposition as Aβ40 and Aβ42 were reduced in parallel. The CSF:serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS.
authors.affiliation: From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK. pashtun.shahim@neuro.gu.se.
authors.forename: Pashtun
authors.initials: P
authors.lastname: Shahim
authors.affiliation: From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Yelverton
authors.initials: Y
authors.lastname: Tegner
authors.affiliation: From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Niklas
authors.initials: N
authors.lastname: Marklund
authors.affiliation: From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Kina
authors.initials: K
authors.lastname: Höglund
authors.affiliation: From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.affiliation: From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Brody
authors.affiliation: From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: From the Institute of Neuroscience and Physiology (P.S., K.H., E.P., K.B., H.Z.), Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., K.H., E.P., K.B., H.Z.), Sahlgrenska University Hospital, Mölndal; Division of Medical Sciences, Department of Health Sciences (Y.T.), Luleå University of Technology; Department of Neuroscience, Neurosurgery (N.M.), Uppsala University, Uppsala, Sweden; Washington University School of Medicine (D.L.B.), St. Louis, MO; and Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000293:Adolescent; D000328:Adult; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D056352:Athletes; D001924:Brain Concussion / Q000150:complications; D000071451:Chitinase-3-Like Protein 1 / Q000134:cerebrospinal fluid; D003430:Cross-Sectional Studies; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D038223:Post-Concussion Syndrome / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000473:pathology*; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism; D013223:Statistics as Topic; D013997:Time Factors; D015599:Trauma Severity Indices; D055815:Young Adult
chemical_list: D016229:Amyloid beta-Peptides; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D012709:Serum Albumin; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)