Epigenome-wide association study of cerebrospinal fluid-based biomarkers of Alzheimer’s disease in cognitively normal individuals
Bibliographic record
Abstract
INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are reliable predictors of future AD risk. We investigated whether pre-clinical changes in AD CSF biomarkers are reflected in blood DNA methylation (DNAm) levels in cognitively normal participants. METHODS: We profiled blood-based DNAm with the EPIC array in participants without a diagnosis of cognitive impairment in the Emory Healthy Brain Study (EHBS; N=495) and ADNI (N=122). Their CSF Aβ42, tTau, and pTau levels were quantified using Elecsys immunoassays. We conducted epigenome-wide association studies to assess associations between DNAm and CSF biomarkers of AD. RESULTS: In EHBS, no loci were Bonferroni-significant after adjusting for confounding factors. In ADNI, two loci were significant, but they were not replicated in EHBS. There was little agreement between the top loci from EHBS and ADNI. DISCUSSION: Our study showed little evidence of an association between differential blood-based DNAm and pre-clinical AD CSF biomarkers.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".