Chronic traumatic encephalopathy: fluid biomarkers

Chronic traumatic encephalopathy (CTE) is a neuropathologic condition that has been described in individuals who have been exposed to repetitive head impacts, including concussions and subconcussive trauma. CTE cannot currently be diagnosed during life. Clinical symptoms of CTE (including changes in mood, behavior, and cognition) are nonspecific and may develop after a latency phase following the injuries. Differential diagnosis based solely on clinical features is, therefore, difficult. For example, some younger patients who do not experience the latency phase (i.e., symptoms of CTE may begin while still being exposed to the repetitive head impacts) may be clinically diagnosed with postconcussive syndrome, a vaguely defined condition that is described in a minority of concussed patients. Some older patients whose initial features of CTE include memory and executive dysfunction and progress to impaired activities of daily living may be clinically diagnosed with Alzheimer disease or another dementia. Although concussions are common in athletes and nonathletes, contact/collision sport athletes, such as boxers, American football players, and ice hockey players, are at greater risk of exposure to both concussion and repetitive subconcussive head impacts. Biomarkers for CTE pathophysiology would be of great value to study and improve our understanding of when and how the disease process starts and develops, as well as how it can be prevented or treated. Here, we review the literature regarding fluid biomarkers for repetitive subconcussive impacts, concussion, postconcussive syndrome, and CTE. We also discuss technical issues and potential pathways forward regarding how to move the most promising biomarker candidates into clinical laboratory practice.