The role of serotonin circuit dysregulation in neurobehavioural symptoms of Alzheimer's disease
Bibliographic record
Abstract
BACKGROUND: The dorsal raphe nucleus (DRN) serotonin (5-HT) neurons, which are critical for socioemotional regulation and cognitive function, are among the earliest to exhibit tau pathology in Alzheimer's disease (AD). 5-HT neurons play a pivotal role in mood, social behavior and cognition. Here, we developed a mouse model to study how early tau pathology in DRN 5-HT neurons contributes to the neuropsychiatric symptoms of AD. METHOD: We generated a cre-dependent adeno-associated virus (AAV) to express a phosphorylation-prone form of human tau (hTauP301L) (controls; fluorescent reporter only). We infused the virus into the DRN of Pet1-cre mice, resulting in its specific expression in 5-HT neurons. Four weeks post- infusion, mice underwent a series of behavioral tasks to assess tau-induced changes in socioemotional and cognitive behaviors. A separate group was included in RNA-seq analysis to investigate the mechanisms underlying early tau-induced pathological changes. RESULT: Early pathological tau expression in 5-HT neurons resulted in increased anxiety-like behavior, altered stress coping strategies, female sex-specific abnormal social behavior and mild cognitive impairment. We additionally identified altered molecular markers that may underlie tau-induced early behavioral changes. CONCLUSION: Our findings offer mechanistic insight into the emergence of neuropsychiatric symptoms early in AD progression, highlighting key targets for therapeutic intervention.
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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) | 0.000 | 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".