Environmental Modulation of Early Tau Pathology in Alzheimer's Disease: A Pretangle‐Tau Rat Model
Bibliographic record
Abstract
BACKGROUND: Longitudinal studies implicate environmental factors as critical modulators of Alzheimer's disease (AD) progression. The locus coeruleus (LC), an early site of hyperphosphorylated tau accumulation, provides a unique target for intervention prior to the emergence of neurofibrillary tangles and amyloid plaques. METHOD: Using a rat model expressing pseudophosphorylated human tau (htauE14) in LC neurons, we explored how early- and late-life environmental enrichment or stress affect tau pathology and behavioral outcomes. RESULT: HtauE14 expression heightened anxiety and impaired olfactory discrimination and spatial learning compared to GFP controls. Early enrichment mitigated tau spread, reduced LC inflammation, and elevated hippocampal BDNF levels, while late-life enrichment reduced anxiety and improved exploratory behavior without altering tau pathology. Conversely, late-life stress amplified LC inflammation. Single-nucleus transcriptomics identified widespread htauE14-induced gene expression changes, exacerbated by early stress in female hippocampi, alongside protective effects of early enrichment across neuronal and glial populations. CONCLUSION: These findings underscore the timing-dependent and sex-specific roles of environmental factors in AD pathogenesis, highlighting the importance of targeted interventions.
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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) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".