Traumatic brain injury or head impacts from contact sports are associated with tau astrogliopathy
Bibliographic record
Abstract
Exposure to traumatic brain injury (TBI) and/or repetitive head impacts (RHI) increase the risk of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy neuropathologic change (CTE-NC). Astrocytic tau pathology reminiscent of ageing-related tau astrogliopathy is a component feature of CTE-NC in many cases. Yet the relationship between TBI/RHI exposure and wider tau astrogliopathy, beyond that of CTE-NC, remains poorly characterized. Autopsy-derived material from 556 individuals was selected to include cases with a history of moderate or severe traumatic brain injury (survival >6 months, n = 77) or a history of participation in contact sports (n = 45), for comparison with uninjured controls with (n = 397) or without (n = 37) neuropathologically confirmed neurodegenerative disease. Representative tissue sections from multiple brain regions were then immunostained for hyperphosphorylated tau (p-tau; PHF-1) and assessed in accordance with the harmonized evaluation criteria for ageing-related tau astrogliopathy. PHF-1-immunoreactive thorn-shaped astrocytes were observed more frequently in contact sports participants (75.6%) versus controls with (32.5%; P < 0.001) and without (8.1%; P < 0.001) neurodegenerative disease. In addition, although the prevalence of thorn-shaped astrocytes following moderate/severe TBI (32.5%) was similar to neurodegenerative disease controls, regression analyses demonstrated increased odds of thorn-shaped astrocytes, when adjusting for age and sex (odds ratio 2.42, 95% confidence interval 1.29-4.54). These findings were observed regardless of whether the pathognomonic lesion of CTE-NC was present in the regions examined. Intriguingly, although subpial thorn-shaped astrocytes at sulcal depths were occasionally observed in aged controls with (3.6%) and without (2.8%) neurodegenerative disease, this pathology was considerably more common following RHI/TBI (42.2%; P < 0.001). These findings support a history of RHI or TBI as an independent risk factor for the development of thorn-shaped tau astrogliopathy, over and above ageing-related tau astrogliopathy observed in ageing and wider neurodegenerative disease. Moreover, trauma might be associated with thorn-shaped astrocytes within specific distributions, including the subpial region of the cortical sulcal depths. The clinical significance of these observations will be important to determine.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 teacher head, 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".