P1‐118: Physiological regulation of plasma amyloid‐beta in APP/PS1dE9 mice and mouse lemur primates
Bibliographic record
Abstract
Testing potential drugs against Alzheimer's disease (AD) and understanding the physiopathology of AD require animal models. Biomarkers, such as CSF and plasma amyloid-beta peptide (Abeta), can evaluate the efficacy of these treatments in induced or spontaneous models of AD as well as the evolution of pathology. Understanding physiopathological processes that modulate those biomarkers is however critical. The aim of our study was to assess the effect of factors such as age, sex, genetic background, and the expression of a putative Abeta receptor (the prion protein (PrP)) on plasma Abeta levels in a transgenic (tg) mouse model of amyloidosis and in a primate model of spontaneous cerebral aging: the mouse lemur primate. Plasma Abeta was assessed in double tg APPswe/PS1dE9 mice and in mouse lemur primates. Mice were 4 to 29 months of age and carried three different genetic backgrounds: B6C3F1 (n = 20), C57Bl6 (n = 23) and Swiss (n = 9). Evaluation of PrP effect was performed by crossing APPswe/PS1dE9 mice (B6C3F1/J background) with PrP+/+ and PrP-/-, mice knockout for PrP gene. Mouse lemurs were 1 to 9 years of age (n = 44). Blood samples were collected in EDTA tubes and centrifuged (2000g; 10min, 4°c) in the 15 minutes following the collection. The supernatant was collected in 200μl polypropylene tubes. A cocktail of protease inhibitors (Complete Mini Roche) was added to plasma samples. Plasma Abeta40 and 42 detections were performed using commercial ELISA kits (BioSource). Plasma Abeta was affected by the strain of mice, stressing the importance of choosing the right animal model. However, plasma Abeta was not modulated by age or pathology progression in APPswe/PS1dE9 mice. Next, we studied prion protein (PrP) expression effect on Abeta peptide in APPswe/PS1dE9/PrP mice. We showed that PrP regulated positively plasma Abeta levels in tg mice. Plasma Abeta was not significantly different between young and aged mouse lemurs. Plasmatic Abeta detection in tg mice and mouse lemurs is a simple and very precise tool, and is modulated by genetic background and PrP expression. This tool could follow the effects of potential treatments for 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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.005 | 0.002 |
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".