Astroglial activation and altered amyloid metabolism in human repetitive concussion

Neurology. 2017 Apr 11;88(15):1400-1407. doi: 10.1212/WNL.0000000000003816. Epub 2017 Mar 10.

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Athletes
  • Brain Concussion / complications
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid
  • Cross-Sectional Studies
  • Female
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid*
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Post-Concussion Syndrome / cerebrospinal fluid*
  • Post-Concussion Syndrome / etiology
  • Post-Concussion Syndrome / pathology*
  • Retrospective Studies
  • Serum Albumin / metabolism
  • Statistics as Topic
  • Time Factors
  • Trauma Severity Indices
  • Young Adult

Substances

  • Amyloid beta-Peptides
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glial Fibrillary Acidic Protein
  • Peptide Fragments
  • Serum Albumin
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)