The Inflammatory Signature of RHI in Athletes at Risk of CTE
Bibliographic record
Abstract
Abstract Background There is accumulating evidence that repetitive head impact (RHI) in former contact sports athletes is a risk factor for developing chronic traumatic encephalopathy (CTE) and other neurodegenerative diseases. The pathological link between RHI and neurodegeneration remains unknown. There is increasing evidence that inflammation is one of the physiological responses to RHI 1,2 . Previous studies have demonstrated elevated inflammatory cytokines in blood immediately and years after a concussion 2,3 . The aim of this study was to compare the inflammatory profiles between former professional contact sports athletes with RHI (ExPro) and patients with Alzheimer's disease (AD) and Healthy controls (HC). Method We used a multiplex proximity extension assay (PEA) technology using Olink Explore Inflammation I and II panel to quantify 737 inflammatory proteins in the cerebrospinal fluid (CSF) of 16 ExPro (mean age=60.9+/‐11), 24 AD (mean age 69.1+/‐9), and 6 HC (mean age=57.0+/‐11). We also evaluated CSF Neurofilament Light (NfL) using Single Molecule Array (SIMOA). An ANCOVA (covariate age) was used to compare inflammatory markers between groups and Pearson correlation was used to evaluate relationship of inflammatory markers with NfL. Result There were 87 neuroinflammatory proteins that were significantly different between ExPro, AD and HC. These markers span immune activation, oxidative stress, vascular inflammation, extracellular matrix remodelling, and neuroinflammation. SCRN1 and MDH1 remained significant after FDR correction. SCRN1 is predominantly involved in immune regulation, vesicular trafficking, and stress response while MDH1 is central to metabolic pathways (TCA cycle, redox balance) and plays a role in oxidative stress and metabolic reprogramming. In the ExPro and AD, NfL was correlated with 105 inflammatory markers but after FDR correction was positively correlated with TBCA, LAIR1, KMT1A/CKMT1B, MILR1, ADAMTS1 and GLOD4. These markers play important roles in inflammation, immune regulation, metabolism, and tissue homeostasis. Conclusion Our results provide evidence that distinct inflammatory profiles exist between former contact sports athletes with RHI, patients with AD and HC. As well, we show a relationship between markers of inflammation and neurodegeneration. Identifying specific inflammatory markers relevant to RHI could support the development of targeted therapies to halt neurodegeneration in RHI. 1. Neurology 93(5), e497(2019); 2. Front Neurol 4, 18(2013); 3. Concussion 2(1), CNC30(2017).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".