Sex Steroid Levels and <scp>AD</scp>‐Like Pathology in 3x<scp>T</scp>g<scp>AD</scp> Mice
Bibliographic record
Abstract
Decreases in testosterone and 17β-oestradiol (E(2)) are associated with an increased risk for Alzheimer's disease (AD), which has been attributed to an increase in β-amyloid and tau pathological lesions. Although recent studies have used transgenic animal models to test the effects of sex steroid manipulations on AD-like pathology, almost none have systematically characterised the associations between AD lesions and sex steroid levels in the blood or brain in any mutant model. The present study evaluated age-related changes in testosterone and E(2) concentrations, as well as androgen receptor (AR) and oestrogen receptor (ER) α and β expression, in brain regions displaying AD pathology in intact male and female 3xTgAD and nontransgenic (ntg) mice. We report for the first time that circulating and brain testosterone levels significantly increase in male 3xTgAD mice with age, but without changes in AR-immunoreactive (IR) cell number in the hippocampal CA1 or medial amygdala. The age-related increase in hippocampal testosterone levels correlated positively with increases in the conformational tau isoform, Alz50. These data suggest that the over-expression of human tau up-regulate the hypothalamic-pituitary-gonadal axis in these mice. Although circulating and brain E(2) levels remained stable with age in both male and female 3xTgAD and ntg mice, ER-IR cell number in the hippocampus and medial amygdala decreased with age in female transgenic mice. Furthermore, E(2) levels were significantly higher in the hippocampus than in serum, suggesting local production of E(2). Although triple transgenic mice mimic AD-like pathology, they do not fully replicate changes in human sex steroid levels, and may not be the best model for studying the effects of sex steroids on AD lesions.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| 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 teacher head, 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".