Investigating the Underlying Mechanisms of Chemosensory Dysfunctions in Alzheimer's Disease Using <i>Caenorhabditis elegans</i> with Mutations in Presenilin 1
Bibliographic record
Abstract
Background Many cases of familial Alzheimer's disease (FAD) are linked to mutations of the presenilin ( PS ) genes. These genes are orthologous with sel‐12 genes in Caenorhabditis elegans , a transparent roundworm. C.elegans have a small nervous system consisting of 302 neurons, making it an ideal candidate for system‐level genetic analysis of neural circuits and behavior. Olfactory dysfunction is an early symptom of AD. However, the underlying mechanisms of these dementia‐linked deficits are unknown. Methods Chemotaxis experiments were conducted on worms with a mutation in sel‐12 to gain a better understanding of the relationship between presenilin 1 ( PS1 ) mutations in AD and olfactory deficits . To understand this phenomenon further, we examined various stages of the worm's life cycle to determine when this deficit appeared. This provided preliminary insight into the dynamics of PS1 mutations and its subsequent effect on cellular pathways involved in chemosensation. Since C. elegans are innately repulsed by the odorant octanol and attracted by the odorant diacetyl, we utilized these two odorants in chemotaxis assays to assess the olfactory function of sel‐12 mutants. Results Adult sel‐12 mutants had a significantly decreased sensitivity to octanol and diacetyl compared to wild‐type worms. Introducing human wild‐type PS1 into the nervous system of C. elegans rescued olfactory defects, while a PS1 mutant from Alzheimer's patients did not. Moreover, C. elegans sel‐12 mutants presented olfactory deficits from hatching, and this deficit increased as worms aged, similar to the neurodegenerative progression of AD. Conclusions This study demonstrates that mutations in C. elegans orthologue of PS1 are associated with altered chemosensation, and that these deficits were rescued by the wild‐type human PS gene in the nervous system. Future Directions In order to localize the region(s) where wild‐type sel‐12 function is required for normal olfaction, sel‐12 and PS1 rescues will be conducted in specific neurons that are responsible for the detection of octanol and diacetyl. We will also investigate the morphology of these neurons and compare them to those of wild‐type worms.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".