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The 2025 Leon Thal Summit convened an international panel of clinicians, neuroscientists, neuropathologists, and neuroimaging specialists to evaluate the current state of biomarker development for chronic traumatic encephalopathy (CTE) and to outline priorities for advancing translational research for this important area. Discussions integrated emerging findings from longitudinal cohorts, new molecular and neuroimaging approaches, expanding post mortem evidence, and evolving insights into exposure biology and genetic modifiers. Consensus themes emphasized the need for biomarkers that detect CTE-specific tau proteoforms, integration of existing imaging and fluid markers into traumatic encephalopathy syndrome research criteria, and refinement of multimodal magnetic resonance imaging and blood-based tools that capture early CTE pathology. The group underscored the importance of coordinated, longitudinal clinicopathological studies and collaborative research frameworks to validate candidate biomarkers and accelerate progress toward accurate diagnosis, disease monitoring, and therapeutic development for individuals at risk for or exhibiting signs of CTE.
There is no validated fluid biomarker for CTE.
a narrative synthesis consistently distinguishes candidate markers from validated CTE-specific tests
Overall, results indicate that small elevations in tracer uptake may occur in regions such as the superior frontal and medial temporal cortices, but these are not sufficient to reliably indicate CTE pathology at the individual patient level.
small cohort and autoradiographic findings consistently show inadequate individual-level specificity
There was general agreement that [repurposing AD amyloid/tau fluid and imaging methods] has not yielded sufficient specificity for CTE.
cross-modal negative findings support the direction, but literature selection was not systematic
Derived from the full evaluation — not a separate score.
Strengths
The Temporal Dynamics section links acute injury, neuroinflammation, evolving tau pathology, atrophy, and co-pathologies to different phases of the proposed CTE continuum. This supplies a useful organizing framework for selecting biomarker purposes and study designs.
↳ Temporal Dynamics of Biomarker Utility Across the CTE Disease Continuum
The PET and Fluid Biomarkers sections state that existing tau PET cannot reliably identify individual CTE pathology, p-tau217 is not CTE-specific, and GFAP evidence lacks external cohort validation. These constraints are generally carried into exploratory rather than clinical recommendations.
↳ Positron Emission Tomography; Fluid Biomarkers; Summary and Recommendations
The report connects named cohorts, federal funders, an Alzheimer's Association interest group, and a proposed permanent research network to longitudinal clinicopathological validation. This gives the research agenda identifiable institutional users and infrastructure.
↳ Introduction; Summary and Recommendations, Recommendation 4
Limitations
The Methods section describes presentations, breakout groups, and SLOB analysis but not how studies were searched, selected, or appraised. Readers therefore cannot determine whether the empirical synthesis is comprehensive or selectively assembled.
↳ Methods
Recommendations are described as reflecting broad consensus and general agreement, but no voting threshold, dissent record, participant-selection analysis, or formal consensus procedure is reported. This limits confidence in how representative the recommendations are.
↳ Methods
The paper discusses autopsy cross-sectionality and validation needs but does not systematically address brain-bank ascertainment or limitations of a CTE-focused summit panel. These omissions matter particularly for genetic and generalizability claims.
↳ Pathology of CTE; Genetics; Methods
The report's strongest feature is its cross-modal synthesis, particularly the Temporal Dynamics framework and the translation of modality-specific limitations into four research recommendations. The score is held near the upper end of the 2.5–3.4 quality band because the Methods section does not report literature identification or selection and gives only a broad description of consensus formation. Clear organization and calibrated wording raise clarity, although the Abstract's early-pathology phrasing is stronger than the body's description of current biomarkers. Impact is most credible through research coordination and funding priorities, not immediate clinical diagnosis.
Nabu’s assessment, alongside the field’s view.
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Sound3.4
Confidence mediumThe report contributes an integrative temporal framework and specific recommendations for exploratory biomarker use in TES research criteria. Its advance remains modest because it supplies no new data or validated marker and primarily organizes an existing research agenda.
Currently available biomarkers should be incorporated into the NINDS consensus research clinical criteria for TES on an exploratory basis
The argument progresses coherently from pathology through imaging, fluids, genetics, disease stage, and recommendations, while repeatedly reporting negative and preliminary evidence. The Methods section does not explain how literature was identified or selected, so a 0.4-point in-band deduction is applied to a merit assessment of 3.6.
Each session consisted of a presentation that reviewed the current literature on the topic
Sectioning and calibrated terms such as exploratory, preliminary, and not yet validated make the main argument easy to follow. Reporting is reduced by the Abstract's early-pathology wording, which is stronger than the Temporal Dynamics account of current biomarker timing.
Most biomarkers currently under investigation in CTE are thought to reflect intermediate or late-stage neurodegenerative changes
The report situates its agenda against TES criteria, named cohorts, comorbid pathologies, autopsy limitations, and the need for clinicopathological validation. It does not systematically examine limitations of the summit process, panel composition, or brain-bank ascertainment, keeping contextual performance below the stronger band.
The CDC-TES has not yet been validated against post mortem findings
Caveats4 of 4 checks
The main conclusions remain interpretable, but two phrases sit uneasily with limitations stated elsewhere in the paper. Both are mitigated by the report's repeated exploratory and preliminary framing.
Relevant financial and professional relationships are extensively disclosed. Ethics approval, preregistration, and data or code availability are not expected for this consensus-oriented narrative review.
Flags: 1 declared / 5 total
50 references in manuscript 50 of 50 checkable references found in an index
No retraction notice found in Retraction Watch.
Sources: Retraction Watch ✓
Where this paper’s evidence sits on the path from initial observation to real-world use.
The recommendations can guide research criteria, funding priorities, and cohort design, but they do not support immediate clinical deployment. The absence of a validated CTE-specific fluid or imaging biomarker leaves translation at an early stage.
There is no validated fluid biomarker for CTE
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