Investigating the Use of [18-F] tau-PET Imaging as a Biomarker of tau Pathology in Retired Athletes at Risk of Neurodegeneration
Bibliographic record
Abstract
The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer’s disease and chronic traumatic encephalopathy. Chronic traumatic encephalopathy is characterized by abnormal accumulation of tau protein in the brains of affected athletes in a pattern distinct from other neurodegenerative diseases. There is currently no in vivo biomarker of tau pathology of chronic traumatic encephalopathy, and the diagnosis is made post-mortem. [18-F] Flortaucipir tau-PET has shown high specificity to tau pathology of Alzheimer’s disease, but studies in chronic traumatic encephalopathy are inconclusive. This study investigated the use of flortaucipir tau-PET in a cohort of former athletes negative for Alzheimer’s disease biomarkers. We first investigated the relationship between genetic risk factors and tau-PET as an indirect measure of tau pathology. We found an association between higher cortical grey matter tau burden as seen with flortaucipir and the APOE4 allele in former athletes. APOE4 allele may be a risk factor for tau accumulation in former contact sports athletes at high risk of neurodegeneration. Next, we investigated the use of phosphorylated tau at threonine 181 (p-tau181) in plasma as an additional biomarker of tau pathology. Although high plasma p-tau181 levels were associated with brain abnormalities, baseline p-tau181 did not predict longitudinal changes in regional brain volumes or white matter integrity in athletes and was at normal levels in a neuropathologically confirmed chronic traumatic encephalopathy case. Plasma p-tau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression. Due to plasma p-tau181 specificity to Alzheimer’s disease pathology, we therefore used it as an additional accessible biomarker to control for presence of Alzheimer’s disease in our cohort. Lastly, we assessed the association of flortaucipir tau-PET with brain volumes in retired athletes; and examined the relationship between tau-PET and neuropsychological functioning. A higher tau-PET signal was associated with reduced grey matter volumes and lower memory scores. Overall, our results show that flortaucipir tau-PET may be useful for identifying neurodegenerative changes in former athletes negative for Alzheimer’s disease pathology. Future neuropathological studies can examine the specificity of flortaucipir to tau pathology of chronic traumatic encephalopathy.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".