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.

创伤性脑损伤 （TBI） 是全世界长期残疾的主要原因。影像学检查和液体生物标志物在预测结局和筛查急性期并发症监测需求方面有用的证据正在稳步增加。尽管如此，许多人在 TBI 的慢性期会出现疲劳、认知和运动功能障碍等症状，此时缺乏对脑损伤的客观评估。创伤性脑病综合征的共识标准是最近才定义的，创伤性脑病综合征是一种可能与神经退行性疾病 慢性创伤性脑病相关的临床综合征，通常与运动脑震荡有关。然而，这些标准并不适合所有患有 TBI 慢性后果的个体。慢性 TBI 的病理生理学与其他神经退行性和神经炎症性疾病（如阿尔茨海默病）有许多相似之处。与阿尔茨海默病一样，液体生物标志物的进步代表了解开病理生理事件链的最有希望的途径之一，以便能够区分这些情况，并随着时间的推移提供预测模型和治疗终点。本综述总结了 TBI 慢性期 （受伤后 ≥6 个月） 的液体生物标志物发现，这些发现表明炎症、神经胶质生物学和神经退行性变与 TBI 的长期并发症有关。我们探讨了生物标志物如何与结果和影像学结果相关联，旨在确定慢性 TBI 和其他神经退行性疾病类型之间生物标志物模式的机制差异。最后，强调了当前局限性和未来液体生物标志物研究的优先领域。