P3‐094: A NOVEL TRANSGENIC RAT MODEL OF TAUOPATHY WITH SEVERE BRAIN ATROPHY, GLIOSIS AND COGNITIVE DEFICITS
Bibliographic record
Abstract
Tauopathies, including Alzheimer's disease and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), display numerous pathologies beyond the neurofibrillary tangles that define this class of disease. Cortical and hippocampal atrophy, ventricular dilation, white matter degeneration, gliosis and frank neuronal loss occur concomitantly with tau pathology, culminating in cognitive deficits and behavioral changes. Although current models of tauopathy have replicated some of these features to varying degrees, there still persists a need for more advanced and comprehensive models that exhibit all these pathophysiological and behavioral phenotypes. We developed a rat model that overexpresses human 4R/2N tau carrying the FTDP-17 mutation, P301S, under the CaMKIIa neuronal promoter. This transgenic line, McGill-R-Tau-P301S, was characterized at multiple time-points using various behavioral, biochemical, immunohistochemical and imaging techniques. Disease-associated phosphorylation and conformation dependent tau immunoreactivity was observed throughout the hippocampus and neocortex from 3 months of age, and progressed in a temporospatial dependent manner. Neuronal loss, cortical thinning and extensive ventricular dilation were present by 18 months of age. In parallel, astrocytic activation and disorganization, as well as pervasive microglia proliferation were observed. Notably, microglia displayed both amoeboid and distinct rod-like microglia morphologies. Additionally, using electron microscopy, we observed axon and myelin degeneration and the occurrence of axonal ballooning. Cognitive decline was detected starting at 18 months of age: rats were impaired in novel object recognition memory, spatial learning and memory, contextual and cued fear conditioning, in the absence of motor deficits. The McGill-R-Tau-P301S rat is a novel model of tauopathy which recapitulates important pathophysiological and behavioral phenotypes associated with human tauopathies. Thus, this model represents a unique and very valuable tool for research in Alzheimer's disease and other tauopathies.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".