Associations between peripheral blood DNA methylation and FDG‐PET signal in AD individuals
Bibliographic record
Abstract
Abstract Background Epigenetics plays a crucial role in regulating genetic transcription and responding to environmental and lifestyle changes without altering the DNA sequence. Their dysregulation is associated with AD, presenting potential as blood biomarkers. However, no study has evaluated whether peripheral blood (PB) epigenetic biomarkers are associated with brain metabolism, indexed by FDG‐PET, a classic Imaging AD biomarker. Thus, we explore the associations between PB DNA methylation and FDG‐PET signal in the brain of cognitively unimpaired (CU) and AD individuals. Method We evaluated CU=43 and AD=122 individuals from the ADNI cohort who underwent FDG‐PET imaging and PB DNA methylation analysis. Methylation data were analyzed using the minfi R package. Correlation analysis was performed with the statistically significant differentially methylated regions (DMRs) (p<0.005) and the regional FDG‐PET standardized uptake value ratio (SUVRs) values extracted with the DKT atlas. Voxel‐wise associations between FDG‐PET and DMRs were tested using linear regressions accounting for group, gender, age, and APOE4 status. The analysis was corrected for multiple comparisons using cluster‐wise RFT (p<0.05). Result We identified 478 DMRs (Figure 1), multiple of them significantly associated with regional FDG‐PET SUVRs (Figure 2). The voxel‐based analysis demonstrated that DMR cg02041677, located in the ATE1 gene, was negatively associated with FDG‐PET signal in the left hippocampus, right orbitofrontal gyrus, and right medial temporal gyrus (tmax=‐4.28, ‐4.04, ‐3.58, respectively; p‐value<0.001). The cg11128212, in the intron, nearby two lncRNA (ENSG00000289046, ENSG00000274591), was positively associated with brain metabolism in the left hippocampus, left temporal pole, and left middle temporal gyrus (tmax=4.08, 3.98, 3.80, respectively; p‐value<0.001) while the cg11901271, located in intron, nearby of a LncRNA (ENSG00000287358), showed positive correlations with FDG‐PET in the Left hippocampus (tmax=5.35, respectively; p‐value<0.001) (Figure 3). Conclusion Here, we show that PB DMRs exhibited a significant pattern of association with brain glucose metabolism in vulnerable AD regions. LncRNAs are important transcriptional regulators, the methylation could impact gene expression in AD and present potential as blood 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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".