P1‐030: Butyrylcholinesterase knockout reduces deposition of fibrillar b‐amyloid in an Alzheimer's mouse model
Bibliographic record
Abstract
Butyrylcholinesterase (BChE) is a serine hydrolase with a variety of enzymatic and non-enzymatic functions. In the normal brain, BChE is expressed in glia, white matter and distinct populations of neurons in areas important for cognition. In Alzheimer's disease, β-amyloid (Aβ) plaques are associated with BChE activity, the significance of which is unclear. A mouse model, containing five human familial Alzheimer's disease genes (5XFAD), also develops Aβ plaques with BChE. To address the unresolved role of BChE in Aβ burden, the 5XFAD mouse was crossed with a BChE-knockout strain (BChE-KO), to produce a 5XFAD/BChE-KO mouse. Brains from the two strains of mouse were cut and stained for total Aβ using immunohistochemistry, fibrillar Aβ using thioflavin-S (Th-S) histofluorescence and for BChE using histochemistry. Plaque loads detected by each of these techniques were quantified and compared in 5XFAD and 5XFAD/BChE-KO at 3 and 6 months. Since sex difference in plaque loads have been observed in human AD as well as AD animal models, female and male mice were analyzed separately. There was no significant difference in the total Aβ plaque load between the 5XFAD and the 5XFAD/BChE-KO mouse strains for females or males at 3 and 6 months of age. There was a trend for reduced total Aβ plaque load in male 5XFAD/BChE-KO mice compared to male 5XFAD mice. However, male 5XFAD/BChE-KO mice at 3 and 6 months of age had significantly less fibrillar Aβ plaque load compared to the corresponding male 5XFAD mice. The diminished fibrillar Aβ plaque deposition in the absence of BChE suggests a role for this enzyme in modulating Aβ pathology.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.009 | 0.003 |
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".