Association of Plasma Biomarker Levels With Their CSF Concentration and the Number and Severity of Concussions in Professional Athletes

OBJECTIVE: To examine whether the brain biomarkers total-tau (T-tau), glial fibrillary acidic protein (GFAP), and β-amyloid (Aβ) isomers 40 and 42 in plasma relate to the corresponding concentrations in cerebrospinal fluid (CSF), blood-brain barrier integrity, and duration of post-concussion syndrome (PCS) due to repetitive head impacts (RHI) in professional athletes. METHOD: In this cross-sectional study, professional athletes with persistent PCS due to RHI (median of 1.5 years after recent concussion) and uninjured controls were assessed with blood and CSF sampling. The diagnosis of PCS was based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). The athletes were enrolled through information flyers about the study sent to the Swedish hockey league (SHL) and the SHL Medicine Committee. The controls were enrolled through flyers at University of Gothenburg and Sahlgrenska University Hospital, Sweden. The participants underwent lumbar puncture and blood assessment at Sahlgrenska University Hospital. The main outcome measures were history of RHI and PCS severity (PCS> 1 year versus PCS< 1 year) in relation to plasma and CSF concentrations of T-tau, GFAP, Aβ40, and Aβ42. Plasma T-tau, GFAP, Aβ40, and Aβ42 were quantified using an ultrasensitive assay technology. RESULTS: A total of 47 participants (28 athletes [median age 28 years, range 18-52] with persistent PCS, due to RHI and 19 controls [median age, 25 years, range 21-35]) underwent paired blood and cerebrospinal fluid (CSF) sampling. T-tau, Aβ40 and Aβ42 concentrations measured in plasma did not correlate with the corresponding CSF concentrations, while there was a correlation between plasma and CSF levels of GFAP (r=0.45, p=0.020). There were no significant relationships between plasma T-tau, GFAP, and blood-brain barrier integrity as measured by CSF:serum albumin ratio. T-tau, GFAP, Aβ40, and Aβ42 measured in plasma did not relate to PCS severity. None of the markers measured in plasma correlated with number of concussions, except decreased Aβ42 in those with higher number of concussions (r=-0.40, p=0.04). CONCLUSIONS: T-tau, GFAP, Aβ40 and Aβ42 measured in plasma do not correspond to CSF measures, and may have limited utility for the evaluation of the late effects of RHI, compared with when measured in CSF. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in professional athletes with post-concussion symptoms, plasma concentrations of T-tau, GFAP, Aβ40, and Aβ42 are not informative in the diagnosis of late effects of repetitive head injuries