Pashtun Shahim1, Yelverton Tegner2, Niklas Marklund2, Kina Höglund2, Erik Portelius2, David L Brody2, Kaj Blennow2, Henrik Zetterberg2. 1. 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. 2. 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.
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.
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.
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