Caspase activation and inflammation observed in the olfactory bulb of APOE4 transgenic mice
Bibliographic record
Abstract
Abstract Background Alzheimer disease (AD) is a chronic neurodegenerative disorder that affects millions of individuals worldwide. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may lead to the discovery of biomarkers and/or treatments for neurodegenerative diseases. Objectives: To characterize the olfactory system in a murine model expressing a genetic risk factor for AD. We investigated olfactory brain region atrophy as well as caspase expression and tissue inflammation in the APOE4 mouse model of AD. Method We assessed the olfactory system in 12 month old wild type (WT) and APOE4 olfactory bulb (OB) for atrophy, caspase activation, markers of neurogenesis and inflammation. We used Western blotting, RT‐PCR and immunohistochemistry. Result There was a significant decrease in OB bulb weight in APOE4 mice compared to WT (p<0.01). There was a significant increase in the full length (p<0.05) form of caspase‐8 and in the p30 fragment (p<0.05) in the APOE4 OB. Moreover, a trend increase in caspase‐8 mRNA (p=0.08) and significant increase in caspase‐9 mRNA in the APOE4 OB vs. WT. Furthermore, there was a decrease in the expression of the mature neuronal marker NeuN in the OB of the APOE4 mice compared to WT. This was with both the 46kDa (p<0.05) and 48kDa (p<0.05) isoforms of NeuN. As atrophy was observed in the APOE4 OB we then assessed for inflammation. Using the IBA‐1 marker for microglia demonstrated that there was a significant increase in IBA‐1 expression (p<0.01) and a trend increased in IBA‐1 positive cells (p=0.054) in the APOE4 OB compared to WT Conclusion These data suggest that there are alterations in neurogenesis in the OB of human APOE4 transgenic mice in addition to inflammation. This corresponds well with what has been observed in human AD brain tissue. Caspase activities detected may play a role in the inflammation observed. Studying the olfactory system in the aging population may help to discover biomarkers in the early stages of AD
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".