SynthesisAlzheimer's research & therapy2022
Distinct sex-specific DNA methylation differences in Alzheimer's disease.
Synthesis in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- The aging epigenome: integrative analyses reveal intersection with Alzheimer's disease.GeroScience · 2026Pooled it
- Pooled it
- A systematic review and meta-analysis of cognitive and behavioral tests in rodents treated with different doses of D-ribose.Frontiers in aging neuroscience · 2022Pooled it
- Blood DNA Methylation Predicts Long-Term Risk of Dementia in Prospective Cohorts.medRxiv : the preprint server for health sciences · 2026Article
- Epigenome-wide DNA methylation patterns associated with disease activity in systemic lupus erythematosus.Scientific reports · 2026Article
- DNA methylation signature of cognitive reserve moderates CSF tau pathology in prodromal Alzheimer's disease.Research square · 2026Article
- Consideration of sex as a biological variable over the history of the 5xFAD Alzheimer's Disease mouse model.Biology of sex differences · 2025Article
- Association of blood-based DNA methylation of lncRNAs with Alzheimer's disease diagnosis.Clinical epigenetics · 2025Article
- Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis.iScience · 2025Article
- Sex-Specific Differential DNA Methylation in Mild Cognitive Impairment and Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- DNA methylation signature of a lifestyle-based resilience index for cognitive health.Alzheimer's research & therapy · 2025Article
- Blood DNA methylation signature for incident dementia: Evidence from longitudinal cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Review
- Research on Prediction of Multiple Degenerative Diseases and Biomarker Screening Based on DNA Methylation.International journal of molecular sciences · 2025Article
- Critical evaluation of the reliability of DNA methylation probes on the Illumina MethylationEPIC v1.0 BeadChip microarrays.Epigenetics · 2024Article
- Inflammation and DNA methylation in Alzheimer's disease: mechanisms of epigenetic remodelling by immune cell oxidants in the ageing brain.Redox report : communications in free radical research · 2024Review
- MIAMI-AD (Methylation in Aging and Methylation in AD): an integrative knowledgebase that facilitates explorations of DNA methylation across sex, aging, and Alzheimer's disease.Database : the journal of biological databases and curation · 2024Article
- Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- DNA methylation in amyotrophic lateral sclerosis: where do we stand and what is next?Epigenomics · 2024Article
- Critical evaluation of the reliability of DNA methylation probes on the Illumina MethylationEPIC BeadChip microarrays.Research square · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSex is increasingly recognized as a significant factor contributing to the biological and clinical heterogeneity in AD. There is also growing evidence for the prominent role of DNA methylation (DNAm) in Alzheimer's disease (AD).
methodsWe studied sex-specific DNA methylation differences in the blood samples of AD subjects compared to cognitively normal subjects, by performing sex-specific meta-analyses of two large blood-based epigenome-wide association studies (ADNI and AIBL), which included DNA methylation data for a total of 1284 whole blood samples (632 females and 652 males). Within each dataset, we used two complementary analytical strategies, a sex-stratified analysis that examined methylation to AD associations in male and female samples separately, and a methylation-by-sex interaction analysis that compared the magnitude of these associations between different sexes. After adjusting for age, estimated immune cell type proportions, batch effects, and correcting for inflation, the inverse-variance fixed-effects meta-analysis model was used to identify the most consistent DNAm differences across datasets. In addition, we also evaluated the performance of the sex-specific methylation-based risk prediction models for AD diagnosis using an independent external dataset.
resultsIn the sex-stratified analysis, we identified 2 CpGs, mapped to the PRRC2A and RPS8 genes, significantly associated with AD in females at a 5% false discovery rate, and an additional 25 significant CpGs (21 in females, 4 in males) at P-value < 1×10
conclusionsOverall, our results show that the DNA methylation differences in AD are largely distinct between males and females. Our best-performing sex-specific methylation-based prediction model in females performed better than that for males and additionally included estimated cell-type proportions. The significant discriminatory classification of AD samples with our methylation-based prediction models demonstrates that sex-specific DNA methylation could be a predictive biomarker for AD. As sex is a strong factor underlying phenotypic variability in AD, the results of our study are particularly relevant for a better understanding of the epigenetic architecture that underlie AD and for promoting precision medicine in AD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.