Blood and cerebrospinal fluid biomarkers

Sports-related traumatic brain injuries (TBIs) range in severity from severe to subconcussive. Although technologies exist for clinical diagnosis of more severe injuries, methods for diagnosis of milder forms of brain injury are limited. Developing objective measures to indicate pathogenic processes after a suspected mild TBI is challenging for multiple reasons. The field of biomarker discovery for diagnosing TBI continues to expand, with newly identified candidate biomarkers being reported regularly. Brain-specific biomarkers include proteins derived from neurons and glia, and are often measured to assess neural injury and repair, and to predict outcomes. Ideally, changes in biomarker levels should indicate pathologic events and answer critical questions for accurate diagnosis and prognosis. For example, does the presence or a change in the biomarker level suggest greater vulnerability for sustaining a second concussion or show that the window of increased vulnerability has passed? Likewise, do changes in biomarker levels predict postconcussion syndrome or recovery/repair? Although there are numerous promising candidates for fluid biomarkers that may diagnose mild TBI or concussion, none has reached the clinic to date. In this chapter, we will define biomarkers, discuss the importance of understanding their normal and pathologic functions, and outline some considerations for interpreting detection assay results in TBI. We will then review five proposed blood and cerebrospinal fluid biomarkers (tau, neurofilament, ubiquitin carboxyl-terminal hydrolase L1, S100β, and glial fibrillary acidic protein) used currently to address TBI. Lastly, we will discuss a future trajectory for developing new, clinically useful fluid biomarkers.