Common Genetic Variants in CHRNA5 Alter β-amyloid Neuropathology and Highlight Chandelier Cells in Human Aging and Alzheimer’s Disease
Bibliographic record
Abstract
Changes in high-affinity nicotinic acetylcholine receptors are connected to cognitive impairment in Alzheimer’s Disease (AD). The nicotinic α5 subunit (coded by CHRNA5) is important for attention and cognition, however its role in the context of aging and neuropathology is unknown. Here, we investigate, in an aged human cohort, the impact two common CHRNA5 polymorphisms: the function-compromising rs16969968 and the expression-altering rs1979905. We observed a significant negative association between the high CHRNA5-expression rs1979905A2 genotype and β-amyloid load. Furthermore, we found that the greatest abundance of CHRNA5 expression was in chandelier cells, a specialized set of interneurons enriched for β-amyloid-binding genes. Finally, we found that in subjects homozygous for the minor allele of the CHRNA5 function-compromising polymorphism rs16969968, chandelier cell proportions in the prefrontal cortex are significantly decreased at high levels β-amyloid levels. Taken together, these findings urge further investigation into the role of CHRNA5 and chandelier cells in AD neuroprotection.
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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) | 0.000 | 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) | 0.004 | 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".