Human Brain Contusions Contain Pathogenic Transmissible Species that Induce Progressive Cognitive Decline and Tau Pathology in Mice
Bibliographic record
Abstract
Objective Traumatic brain injury (TBI) is an established risk factor for dementia, although the underlying mechanisms remain unclear. Our previous research demonstrated that a single severe TBI in wild‐type (WT) mice induces a prion‐like form of tau (tau TBI ) that spreads throughout the brain, leading to memory deficits. Here, we investigated whether similar self‐propagating tau TBI conformers are generated in humans after severe TBI. Methods We biochemically assessed tau and phosphorylated tau (P‐tau) levels in human brain contusions surgically removed acutely after severe TBI. Inoculation studies were performed using human TBI brain homogenates in WT and tau knockout (KO) mice to investigate the role of endogenous tau in tau TBI propagation. Cognitive function was evaluated using the novel object recognition test, the radial arm water maze, and the Y‐maze. Pathological changes in the brain of the inoculated mice were analyzed by histological and biochemical analyses, and targeted transcriptomics. Results Inoculation of human TBI brain homogenates in WT mice caused widespread tau deposition and cognitive impairment, hippocampal synaptic loss, and disease‐associated transcriptomic changes. Effects were similar upon secondary inoculation in WT but not tau KO mice, confirming a tau‐dependent mechanism. Interpretation Severe TBI induces transmissible tau TBI conformers in humans acutely after injury, potentially exacerbating post‐traumatic pathology, and increasing the risk for dementia later in life. ANN NEUROL 2026;99:897–911
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".