{"id":"doi:10.3390/neurolint18100195","kind":"review","title":"Fluid Biomarkers for the Antemortem Detection of Chronic Traumatic Encephalopathy: A Critical Review","authors":["Shatirishvili N"],"author_count":1,"year":2026,"published":"2026-10-17","venue":"Neurology international","cited_by":0,"doi":"10.3390/neurolint18100195","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.3390/neurolint18100195","archive_url":"https://space-kitty.com/papers/doi:10.3390/neurolint18100195","updated":null,"pmid":"42931149","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Chronic traumatic encephalopathy (CTE) is a progressive tauopathy associated with repetitive head impacts (RHIs) and is currently confirmed only at autopsy. The absence of a validated antemortem diagnostic limits individual risk assessment, clinical trial enrollment, and differentiation from disorders such as Alzheimer's disease (AD). This review critically evaluates five candidate fluid biomarkers: phosphorylated tau (p-tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), and soluble TREM2 (sTREM2). For each, the review assesses the biological mechanism, CTE/RHI-specific evidence, diagnostic performance, and major confounders. None currently provides CTE-specific discrimination. In the largest cohort, plasma p-tau217 tracked amyloid status rather than CTE pathology. NfL reflects axonal injury but is nonspecific and strongly age-dependent. GFAP is associated with clinical CTE certainty in football and combat-sport cohorts, although not in an independent rugby cohort. S100B responds acutely to head impacts without a persistent cumulative signal. sTREM2 may reflect microglial activation that is bidirectionally related to tau after RHI exposure, but its primary case-control comparison was null. Short study windows may also be poorly matched to CTE's multi-decade latency, and most evidence for p-tau, NfL and GFAP derives from one cohort, with the total tau, extracellular-vesicle and sTREM2 findings from a second. The review therefore emphasizes multi-marker panels, assay standardization, and longitudinal antemortem-to-autopsy cohorts as the validation work required before any fluid biomarker can support antemortem CTE detection.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Fluid Biomarkers for the Antemortem Detection of Chronic Traumatic Encephalopathy: A Critical Review\" by Shatirishvili N, https://doi.org/10.3390/neurolint18100195, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"neurodegeneration","name":"Alzheimer's, Parkinson's & Neurodegeneration","domain_slug":"medicine"}],"cited_in_dossiers":[]}