Phosphothreonine175 and Phosphothreonine231 Expression in Chronic Traumatic Encephalopathy (CTE) and Chronic Traumatic Encephalomyelopathy - Therapeutic Implications (S11.004)
Bibliographic record
Abstract
Objective: To characterize the tauopathy of chronic traumatic encephalopathy (CTE) and compare this to the pathological tau phosphorylation observed in amyotrophic lateral sclerosis with cognitive impairment (ALSci). Background: CTE is a rapidly progressive neurodegenerative disease associated with head trauma, and characterized by widespread accumulation of aberrantly phosphorylated microtubule associated protein tau (tau). 10[percnt] of patients develop motor dysfunction consistent with ALS (CTEM). ALSci tau has been characterized by aberrant phosphorylation at Thr175 (pThr175) and the inclusion of all 6 isoforms in the insoluble fraction. Toxicity of pThr175 tau has been associated with increased GSK3β activation and phosphorylation of Thr231. Due to vulnerable neuronal population overlap with ALSci and common pathology, tau protein dysregulation may share one toxic process in CTE and ALSci. Design/Methods: CTEM (n=5), CTE (n=5), and control (n=5) brain tissue slides were obtained from the Boston University Brain Bank. Hippocampal formation and spinal cord slides were stained with antibodies for tau (pThr175 and pThr231), GSK3β (pTyr216), and TDP-43 and analyzed by light microscopy. Tau protein from temporal pole and anterior cingulate cortex from 6 stage III CTE cases was isolated and separated into soluble and insoluble fractions. Isolated protein was analyzed by western blot and probed for pThr175, total tau, 3R and 4R tau. Results: All 6 tau isoforms were present in the insoluble fraction in western blots probed for pThr175 and total tau. Histological analysis revealed punctate and fibrillar inclusions accompanied by neuritic pathology in the hippocampal formation in all CTE and CTEM cases. Controls lacked neuritic or fibrillar pathology, though punctate staining was observed. CTE and CTEM cases contained tau pathology in spinal motor neurons. Conclusions: There is evidence of overlapping pathological processes in ALSci and CTE. GSK3β inhibition may be a therapeutic avenue in both disorders. supported by the Ontario Neurodegenerative Disease Research Initiative
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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 | 0.000 | 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) | 0.003 | 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".