Bibliographic record
Abstract
BACKGROUND: Alzheimer's disease (AD) affects both grey and white matter, leading to axonal degeneration, demyelination and glial pathologies. This study investigates the impact of pathological hyperphosphorylated tau (p-Tau) on axonal damage and on demyelination and remyelination process in the Alzheimer's-like tauopathy rat model in vivo. METHOD: We utilized the newly generated McGill-R955-hTau transgenic (Tg) rats expressing the longest human tau isoform with the P301S mutation. Cognitive function was assessed through behavioral testing. Tau expression patterns in grey and white matter were mapped using immunohistochemistry. Axonal damage and myelin pathology were examined via electron microscopy, and oligodendrocyte marker expression profiles were analyzed through immunohistochemistry. RESULT: Tg rats exhibited age-dependent progression of p-Tau levels, spreading from neuronal cell bodies in grey matter to axonal tracts and oligodendrocyte cytoplasm in white matter. This progression resulted in cognitive impairments, neurodegeneration, as well as axon and myelin loss. Ultrastructural analysis revealed extensive axonal and myelin degeneration characterized by swollen myelinated axons, empty myelin sheaths, splitting of myelin lamellae, formation of myelin balloons, and concentric membranous whorls. Myelin debris were observed in microglia and astrocytes. Following white matter demyelination, we found that oligodendrocyte progenitor cell (OPC) differentiated more efficiently in Tg rats than wild type (Wt) rats, however did not translate into increased remyelination due to increased axonal degeneration in Tg rats compared to Wt rats. CONCLUSION: Our findings suggest that axonal damage caused by abnormal tau accumulation and phagocytosis by microglia and astrocytes can lead to myelin pathology and loss. The resulting demyelination may signal OPCs to differentiate to facilitate remyelination.
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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 | 0.000 |
| 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 | 0.001 |
| 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 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".