Chronic traumatic encephalopathy is a neurodegenerative tauopathy associated with exposure to repetitive head impacts, particularly in contact sports. Despite well-defined neuropathological criteria, in vivo identification remains a major challenge. This narrative review synthesizes current evidence on candidate biomarkers of chronic traumatic encephalopathy, integrating findings from neuroimaging, fluid-based, and multimodal studies in repetitive head impact–exposed populations such as contact sport athletes. Key pathophysiological processes, including axonal injury, neurovascular dysfunction, neuroinflammation, and tau aggregation, provide a framework for interpreting biomarker findings, although their temporal and causal relationships remain incompletely understood. Neuroimaging studies have identified group-level structural and molecular alterations, such as regional atrophy and heterogeneous tau positron emission tomography signal, without consistent associations with clinical syndromes. Fluid biomarkers reflecting tau-related processes, axonal injury, glial activation, inflammation, and metabolic changes have shown variable results across studies, often with small effect sizes and substantial overlap between exposed and control groups. Multimodal approaches suggest that a subset of individuals may exhibit measurable biological alterations, although their clinical relevance remains uncertain. Clinicopathological studies indicate associations between in vivo findings and underlying tau pathology at the group level, while also demonstrating overlap with other neurodegenerative conditions. Current evidence reflects biological changes associated with repetitive head impact exposure but remains heterogeneous, and is largely derived from cross-sectional studies in selected populations. At present, available biomarkers do not allow consistent differentiation between markers of exposure, nonspecific injury, and underlying neuropathological processes.
Berrios et al. (Fri,) studied this question.