HIVEP3 variant is associated with increased amyloid deposition and lower hippocampal volume in cognitively unimpaired subjects.
Bibliographic record
Abstract
Abstract Background A GWAS performed in a Canadian cohort identified, for the first time, the polymorphism rs10493098 C in the HIVEP3 gene to be associated with increased risk for late‐onset Alzheimer’s disease (AD). HIVEP3 is a transcription factor that regulates inflammatory response, neuroregeneration, cell growth and apoptosis. In this project, we examined three different population cohorts (PREVENT‐AD, ROSMAP and ADNI cohorts) to investigate the role of the rs10493098 C polymorphism in the pathophysiology of AD. Method In the PREVENT‐AD cohort, 18F‐NAV4694 PET was used to measure amyloid burden, and participants were followed for at least four years. In the autopsied‐confirmed ROSMAP cohort, Aß load and NFT density in the cortex were measured by immunohistorychemistry. Participants were followed throughout most of their adult life, until death. In the ADNI cohort, hippocampal volume was assessed with magnetic resonance imaging, and we evaluated follow‐up for 1 year. Result In the Prevent‐AD cohort, participants who are homozygous for the HIVEP3 C variant had higher amyloid index score compared to non‐carriers (p=0.004) (Fig 1). There is an interaction between APOE4 and HIVEP3, and participants who are APOE4 positive and homozygous for the HIVEP3 C variant exhibit even higher amyloid deposition compared to non‐carriers (p<0.001) (Fig 1). Participants who are homozygous for the HIVEP3 C variant have a higher risk of having an amyloid positive scan than participants who are non‐carriers (p=0.04) (Fig 1). There was no association between the HIVEP3 rs10493098 C variant and Braak or Cerad stages in the ROSMAP population. In the ADNI cohort, considering only the participants who had normal cognition, subjects who are homozygous for the HIVEP3 rs10493098 C variant display lower right hippocampus volume compared to heterozygous and non‐carriers (p=0.032) (Fig 2). Conclusion The HIVEP3 rs10493098 C variant is associated with higher amyloid deposition and lower hippocampal volume in cognitively unimpaired individuals
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".