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Astroglial activation and altered amyloid metabolism in human repetitive concussion

Shahim, Pashtun ; Tegner, Yelverton ; Marklund, Niklas LU orcid ; Höglund, Kina ; Portelius, Erik ; Brody, David L ; Blennow, Kaj LU and Zetterberg, Henrik LU (2017) In Neurology 88(15). p.1400-1407
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,... (More)

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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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Journal Article
in
Neurology
volume
88
issue
15
pages
1400 - 1407
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85018646525
  • pmid:28283595
ISSN
1526-632X
DOI
10.1212/WNL.0000000000003816
language
English
LU publication?
no
id
b92c13e4-da08-4ca7-8fea-e218ee358753
date added to LUP
2017-04-11 10:46:36
date last changed
2024-08-19 20:11:42
@article{b92c13e4-da08-4ca7-8fea-e218ee358753,
  abstract     = {{<p>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.</p><p>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).</p><p>RESULTS: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS &gt;1 year. Athletes with PCS &gt;1 year had higher RPQ scores and number of concussions than athletes with PCS &lt;1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS &gt;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.</p><p>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.</p>}},
  author       = {{Shahim, Pashtun and Tegner, Yelverton and Marklund, Niklas and Höglund, Kina and Portelius, Erik and Brody, David L and Blennow, Kaj and Zetterberg, Henrik}},
  issn         = {{1526-632X}},
  keywords     = {{Journal Article}},
  language     = {{eng}},
  number       = {{15}},
  pages        = {{1400--1407}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Neurology}},
  title        = {{Astroglial activation and altered amyloid metabolism in human repetitive concussion}},
  url          = {{http://dx.doi.org/10.1212/WNL.0000000000003816}},
  doi          = {{10.1212/WNL.0000000000003816}},
  volume       = {{88}},
  year         = {{2017}},
}