P3–016: Characterization of a transgenic model of Alzheimer's disease: The influence of <i>Npas4</i> gene expression on the development of the pathology
Bibliographic record
Abstract
In the present study, we characterize the McGill Thy1-APP transgenic model of Alzheimer's disease, (over-expressing the human amyloid precursor protein with the Swedish and Indiana mutations) through genetic expression and electrophysiology recordings. The Npas4 gene was selected because it's importance for memory formation, neuronal plasticity and influence over long term potentiation. Analysis of the expression of the memory related Npas4 gene was conducted at three months (n=3 controls and 3 Tg) and five months (n=4 controls and 4 Tg) of age. In brief, total RNA was isolated from dissected hippocampus for synthesis of single-stranded cDNA library, later used as template in a real-time quantitative PCR. Changes in gene expression were reported as percent changes relative to controls. In order to test whether Tg mice presented impaired early long-term potentiation in vitro, acute brain slices (n= 4 controls and 4 Tg) of 5-month old Tg mice were submitted to theta burst stimulation and fEPSP slopes were evaluated 40 minutes after. Our results shown that expression of the Npas4 gene was decreased in the Tg analyzed model when compared to controls. Even more, as the mice age, lower expression of the Npas4 gene continues and progress (-49 ±0.005% at 3 months and -64±0.005% at five months of age), corroborating with LTP results that presents less potentiation (145.02±8.8%) in the Tg mice when compared to controls (207.93±18.7%). This results associate with the information that this gene is relevant to prevent/avoid neurodegeration as aging and its impairment in this the analyzed model can be associated with the evolution of the disease in Alzheimer's patients. In summary, we propose a novel molecular marker in the evolution of the phenotype of the Alzheimer disease that can show early changes before clinical symptoms appear and up-regulation of Npas4 in the brain can improve the outcome of the disease.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| 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".