P1‐067: Age‐, sex‐ and transgene‐dependent biphasic alterations of social behavior in triple‐transgenic 3XTg‐AD mice
Bibliographic record
Abstract
Beside memory deficits, Alzheimer's disease (AD) progressively induces alteration of social interactions, personality changes and, at a later stage, apathy. On the other hand, higher incidence of AD was reported in women compared to men. Behavior/immunoblots/ELISAs. Here, we investigated the evolution of social behavior in 3xTg-AD mice harboring presenilin (PS1) (M146V)knockin, APPswe, and tau(P301L) transgenes. Social interactions between 3xTg-AD mice and age- and sex-paired related non-transgenic control littermates (NonTg) were investigated in 12-month-old males, 18-month-old males, 12-month-old females and 18-month-old females. While no difference was observed at 12 months, 3xTg-AD males displayed a drastic increase of their social interactions at 18 months compared to NonTg, suggesting social disinhibition. This marked increase in social interactions was seen earlier in females, i.e. as soon as 12 month old. In contrast, 18 month-old females presented a strong decrease of their social behavior, akin to apathy. To investigate possible molecular correlates, we measured Abeta and Tau markers of AD pathology in the frontal cortex, a critical region for social behavior. Age-, sex- and transgene-dependent increases in total tau, Abeta40 and Abeta42 were observed in both TBS-soluble and detergent-insoluble fraction from frontal cortex homogenates. Overall, our results indicate that 3XTg-AD mice exhibit age-dependent alterations of social behavior following a time-line matching the accumulation of tau and Abeta in the frontal cortex. The influence of gender was critical as females displayed behavior symptoms and, to a lesser extent, tau / Abeta pathologies earlier than males. The biphasic alterations of social responses (social disinhibition followed by apathy) strongly echoes reported progression of AD psychiatric symptoms.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".