Abstract Details

Title Astroglial activation and altered amyloid metabolism in human repetitive concussion

Topic Neuro Trauma, Critical Care, and Sports Neurology

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 4-056

Objective To determine whether post-concussion syndrome due to repetitive concussive TBI is associated with CSF biomarker evidence of astroglial activation, amyloid deposition and blood-brain barrier (BBB) impairment.

Background Experimental and post-mortem case-control studies suggest that athletes who have been exposed to repetitive head trauma are at increased risk of developing brain pathology, such as Aβ deposition, pathology, and astrogliosis. Whether these changes are present in CSF of living humans who have suffered repetitive head trauma have not been investigated.

Design/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 PCS may be associated with biomarker evidence of astroglial activation and 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/Disclosures
Pashtun Shahim, MD, PhD (Sahlgrenska AcademyNeurochemistry) PRESENTER	No disclosure on file
Kaj Blennow	Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ALZPath. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AriBio. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beckman-Coulter. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BioArctic. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moleac Pte. Ltd. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurimmune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Pharma. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prothena. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quanterix. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Diagnostics. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens Healthineers. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AC Immune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ALZPath. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AriBio. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Beckman-Coulter. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BioArctic. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Moleac Pte. Ltd. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurimmune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharma. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prothena. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Quanterix. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Diagnostics. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Siemens Healthineers. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Julius Clinical. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AC Immune. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Celdara Medical. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Diagnostics. Kaj Blennow has received personal compensation in the range of $500-$4,999 for serving as a Co-founder with Brain Biomarker Solutions.
Henrik Zetterberg (Sahlgrenska University Hospital/Molndal)	Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley and Elsevier. Henrik Zetterberg has stock in Brain Biomarker Solutions.

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