Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer’s dementia
Bibliographic record
Abstract
BACKGROUND: Previous studies have shown that copy number variation (CNV) in the alpha (α)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer's dementia (AD). We have previously demonstrated the presence of α-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain α-amylase activity. METHODS AND MATERIALS: The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 ± 5.9, females 58.2%) from the Malmö diet and cancer study genotyped for AMY1A copy number, whereof 247 where diagnosed with AD during a mean follow-up of 20 years. Associations between AMY1A copy number and cognitive performance where analyzed in 791 individuals (mean age at baseline 54.7 ± 6.3, females 63%), who performed Montreal Cognitive Assessment (MoCA) test. Correlation analysis between α-amylase activity or α-amylase gene expression and AMY1A copy number in post-mortem hippocampal tissue from on demented controls (n = 8) and AD patients (n = 10) was also performed. RESULTS: Individuals with very high ( ≥10) AMY1A copy number had a significantly lower hazard ratio of AD (HR = 0.62, 95% CI 0.41-0.94) and performed significantly better on MoCA delayed word recall test, compared to the reference group with AMY1A copy number 6. A trend to lower hazard ratio of AD was also found among individuals with low AMY1A copy number (1-5) (HR = 0.74, 95% CI 0.53-1.02). A tendency towards a positive correlation between brain α-amylase activity and AMY1A copy number was found, and females showed higher brain α-amylase activity compared to males. CONCLUSION: Our study suggests that the degree of α-amylase activity in the brain is affected by AMY1A copy number and gender, in addition to AD pathology. The study further suggests that very high AMY1A copy number is associated with a decreased hazard ratio of AD and we speculate that this effect is mediated via a beneficial impact of AMY1A copy number on episodic memory performance.
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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 | 0.001 | 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".