Fluid biomarkers of chronic traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of long-term disability across the world. Evidence for the usefulness of imaging and fluid biomarkers to predict outcomes and screen for the need to monitor complications in the acute stage is steadily increasing. Still, many people experience symptoms such as fatigue and cognitive and motor dysfunction in the chronic phase of TBI, where objective assessments for brain injury are lacking. Consensus criteria for traumatic encephalopathy syndrome, a clinical syndrome possibly associated with the neurodegenerative disease chronic traumatic encephalopathy, which is commonly associated with sports concussion, have been defined only recently. However, these criteria do not fit all individuals living with chronic consequences of TBI. The pathophysiology of chronic TBI shares many similarities with other neurodegenerative and neuroinflammatory conditions, such as Alzheimer disease. As with Alzheimer disease, advancements in fluid biomarkers represent one of the most promising paths for unravelling the chain of pathophysiological events to enable discrimination between these conditions and, with time, provide prediction modelling and therapeutic end points. This Review summarizes fluid biomarker findings in the chronic phase of TBI (>= 6 months after injury) that demonstrate the involvement of inflammation, glial biology and neurodegeneration in the long-term complications of TBI. We explore how the biomarkers associate with outcome and imaging findings and aim to establish mechanistic differences in biomarker patterns between types of chronic TBI and other neurodegenerative conditions. Finally, current limitations and areas of priority for future fluid biomarker research are highlighted. Traumatic brain injury can result in long-lasting symptoms and is associated with progressive neurodegenerative and neuroinflammatory pathology, but biomarkers to diagnose and monitor these chronic effects are lacking. Here, Thelin and co-workers summarize the available evidence for fluid biomarker use in chronic traumatic brain injury. Many people live with chronic symptoms following traumatic brain injury (TBI), with an increased risk of developing neurodegenerative conditions.The current definitions of chronic TBI do not cover all aspects of the disease, and biomarkers of neurodegeneration and neuroinflammation have not been included in the diagnostic criteria.Neurofilament light and glial fibrillary acidic protein remain elevated in blood years after brain injury, and elevated tau protein is seen in people with chronic TBI who are developing neurodegenerative conditions.Autoantibodies towards brain-enriched proteins are elevated in blood in both the acute and chronic phases of TBI and are associated with levels of neurodegenerative proteins.Considering the heterogeneity of the existing literature, improved grading of chronic TBI symptomatology and better biomarker sampling strategies are warranted to advance current criteria and guidelines.