Blood-Based Biomarkers in the Diagnosis of Chronic Traumatic Encephalopathy: Research to Date and Future Directions

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease consistently associated with repetitive traumatic brain injuries (TBIs), which makes multiple professions, such as contact sports athletes and the military, especially susceptible to its onset. There are currently no approved biomarkers to diagnose CTE, thus it can only be confirmed through a post-mortem brain autopsy. Several imaging and cerebrospinal fluid biomarkers have shown promise in the diagnosis. However, blood-based biomarkers can be more easily obtained and quantified, increasing their clinical feasibility and potential for prophylactic use. This article aimed to comprehensively review the studies into potential blood-based biomarkers of CTE, discussing common themes and limitations, as well as suggesting future research directions. While the interest in blood-based biomarkers of CTE has recently increased, the research is still in its early stages. The main issue for many proposed biomarkers is their lack of selectivity for CTE. However, several molecules, such as different phosphorylated tau isoforms, were able to discern CTE from different neurodegenerative diseases. Further, the results from studies on exosomal biomarkers suggest that exosomes are a promising source of biomarkers, reflective of the internal environment of the brain. Nonetheless, more longitudinal studies combining imaging, neurobehavioral, and biochemical approaches are warranted to establish robust biomarkers for CTE.