Biomarkers of Neuronal Damage in Repetitive Mild Traumatic Brain Injury
Levels of neurofilament light protein and amyloid β reflect CNS injury after repeated mild traumatic brain injury events.
Elevated levels of neurofilament light proteins and decreased amyloid β in cerebrospinal fluid (CSF) may represent markers of central nervous system (CNS) injury among patients with postconcussive syndrome (PCS), according to a study published in JAMA Neurology.
Although symptoms of mild traumatic brain injury (mTBI) are typically short-lived, up to 15% of patients will develop PCS, or mTBI symptoms that persist beyond 3 months. Some patients who have PCS due to repetitive mTBI will progress to chronic traumatic encephalopathy, a neurodegenerative disorder whose histopathology is similar to that of Alzheimer's disease, involving tau protein hyperphosphorylation and amyloid β deposition. However, the role of neuronal damage in the progression of repeated mTBI to PCS is not well understood.
“Notably, there are no objective biomarkers to quantify neuronal damage or other types of central nervous pathology in individuals with PCS,” the authors, led by Pashtun Shahim, MD, PhD, of the University of Gothenburg in Sweden, wrote.
The researchers evaluated professional Swedish ice hockey players for CSF markers of CNS injury. Of 31 participants, 16 were hockey players with PCS due to repeated mTBI, and 15 were healthy controls with no PCS.
Players who had PCS symptoms for more than 1 year had higher levels of neurofilament light protein, a marker of axonal white matter damage, compared with players whose PCS symptoms resolved within 1 year and normal controls (median, 410 pg/mL vs 210 pg/mL and 238 pg/mL, respectively; P = .04 and P = .02, respectively).
Amyloid β levels were significantly lower in all players with PCS than in controls (median, 1000 pg/mL vs 1094 pg/mL; P = .05). Among players with PCS, amyloid β concentrations did not differ by duration of PCS symptoms.
No significant differences were found in the levels of total tau, phosphorylated tau, glial fibrillary acidic protein (marker of axonal injury), or neurogranin (marker of synaptic degeneration).
Significant correlations were found between neurofilament light protein concentrations and Rivermead Post Concussion Symptoms Questionnaire scores (ρ = 0.58, P = .02) and number of lifetime concussion events (ρ = 0.52, P = .04).
“Increased [CSF] neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition,” the authors concluded. “Measurement of these biomarkers may be an objective tool to assess the degree of [CNS] injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy.”
This study was supported by grants from the Swedish Research Council, the European Research Council, Centrum for Idrottsforskning, the Torsten Soderberg Foundation, the Knut and AliceWallenberg Foundation, and Frimurarestiftelsen.
Henrik Zetterberg, MD, PhD, and Kaj Blennow, MD, PhD, are cofounders of Brain Biomarker Solutions in Gothenburg AB, a University of Gothenburg venture-based platform company at the University of Gothenburg. No other disclosures were reported
Shahim P, Tegner Y, Gustafsson B, et al. Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury. JAMA Neurol. Published online: September 19, 2016. doi:10.1001/jamaneurol.2016.2038.