Association of Blood‐based DNA Methylation Markers with Cognition in Alzheimer’s Disease
Bibliographic record
Abstract
Abstract Background DNA methylation is an epigenetic change characterized by the addition of methyl groups to DNA, typically in the cytosine‐ phosphate‐guanine (CpG) nucleotide base pairings. Given that DNA methylation alterations are shown to be associated with Alzheimer’s Disease (AD) pathology in autopsied brains, blood‐based DNA methylation changes are increasingly being studied as a potential peripheral biomarker for AD. However, the role of blood‐based DNA methylation changes as a marker of cognitive impairment in AD remains unclear. In this study, we aim to identify the blood‐based DNA methylation signatures that are associated with worse cognitive performance and brain atrophy in AD individuals. Methods 277 AD patients of Chinese ethnicity were recruited from a tertiary memory clinic (National Neuroscience Institute, Singapore). All participants underwent the Montreal Cognitive Assessment (MoCA) test and blood collection. CpG probe methylation was measured using the Illumina Infinium MethylationEPIC BeadChip. A subset of participants (n = 218, 78.7%) underwent MRI brain scan and medial temporal lobe atrophy (MTA) score was measured visually. Regression analysis evaluated the associations of each methylation marker with MoCA and MTA scores, corrected for age, gender and years of education. Results We identified two methylation markers (cg11103255 and cg10845701) to be associated with MoCA scores. Hypermethymation at the cg11103255 site was associated with lower MoCA scores (p = 2.86e‐07) while hypomethylation at the cg10845701 site was associated with lower MoCA scores (p = 8.18e‐07). Furthermore, hypomethylation at the cg10845701 site was associated with higher MTA scores. cg11103255 is mapped to the Microtubule Crosslinking Factor 1 (MTCL1) gene, a protein coding gene that enables microtubule binding activity. cg10845701 is mapped to the Solute Carrier Family 44 Member 5 (SLC44A5) gene, a protein coding gene that enables transmembrane transporter activity. While the role of MTCL1 gene on AD is not known, SLC44A5 was previously reported to be associated with brain atrophy in an AD GWAS. Conclusion Our findings demonstrate the potential role of blood‐based DNA methylation markers as measures of worse cognitive performance among AD. Further longitudinal studies in an independent cohort are needed to validate these findings.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".