Sex and Genotype Influence Neural Progenitor Cells in a Sporadic Alzheimer's Disease Model
Bibliographic record
Abstract
BACKGROUND: The three non-modifiable risk factors for Alzheimer's disease (AD) are advancing age, female sex and at least one APOEε4 allele. Females with AD experience more severe cognitive decline and pathological changes in the brain, including faster hippocampal atrophy, greater AD neuropathology, and steeper cognitive decline than males with AD. Notably, female APOEε4 carriers have an even higher risk of developing AD earlier, exhibiting greater cognitive decline and more severe neuropathological outcomes than male APOEε4 carriers at middle age. Hippocampal neurogenesis is altered in AD, and sex differences have been identified. However, the effect of advancing age, sex, and APOE genotype on neurogenesis remains unexplored. Therefore, the current study aims to identify how sex and APOE genotype differently affect the dynamics of neurogenesis, including the expression of neural progenitor cells and the maturation rate of new neurons. METHOD: We used 2-month-old (young adulthood) and 12-month-old (middle age) male and female humanized (h) APOEε3 and hAPOEε4 mice. Newly proliferated cells were labeled with the thymidine analog bromodeoxyuridine (BrdU). Brains were collected either 24 hours, 2 weeks, or 4 weeks after BrdU injection to capture the various stages of neurogenesis. The extracted brains were sectioned and processed for immunohistochemistry to measure the neural progenitor cell pool (BrdU/Sox2), the maturation of new neurons (BrdU/NeuN), and potentially the pluripotency of newly formed putative neural stem cells (BrdU/Sox2-ir). RESULT: Analyses are ongoing, but we expect that hAPOEε4 mice will display different temporal dynamics of neurogenesis compared to hAPOEε3 mice, which will result in different levels of hippocampal neurogenesis. Moreover, interactions between sex and genotype are anticipated, with hAPOEε4 females expected to exhibit a slower neuronal maturation rate compared to other groups. CONCLUSION: Our research findings will reveal the role of sex and genotype in neurogenesis, neuronal maturation and factors influencing the pluripotency of neural stem cells in AD model, providing a better understanding of AD-related neuropathological changes.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".