SynthesisFrontiers in aging neuroscience2021
A Meta-Analysis of Brain DNA Methylation Across Sex, Age, and Alzheimer's Disease Points for Accelerated Epigenetic Aging in Neurodegeneration.
Synthesis in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
56 citing papers in PubMed, 3 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- A cell-type-resolved meta-analysis reveals glial DNA methylation changes associated with aging and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Pooled it
- The aging epigenome: integrative analyses reveal intersection with Alzheimer's disease.GeroScience · 2026Pooled it
- Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer's disease.Alzheimer's research & therapy · 2023Pooled it
- From aging to Alzheimer's disease: concordant brain DNA methylation changes in late life.Genome medicine · 2026Article
- Epigenetic Aging in Brain Tissue of the Self-Fertilizing Vertebrate,Ecology and evolution · 2026Article
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.American journal of human genetics · 2026Article
- Integrative epigenomic landscape of Alzheimer's Disease brains reveals oligodendrocyte molecular perturbations associated with tau.Nature communications · 2026Article
- Astrocyte epigenetics in development, aging, and neurodegeneration: a DNA methylation perspective.Frontiers in molecular neuroscience · 2026Review
- DNA methylation signatures of frailty beyond age: a longitudinal study of female and male mice.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic dysregulation of transposable elements in cognitive impairment and Alzheimer's disease.GeroScience · 2025Article
- Do Glioma Cells Rewire Neural Circuits through Epigenetic Changes? DNA Methylation Analysis of Genes Involved in Neuron-Glioma Communication in the Human Frontal Cortex.Journal of molecular neuroscience : MN · 2025Article
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.bioRxiv : the preprint server for biology · 2025Article
- Long-read sequencing reveals genomic and epigenomic variation in the dark genome of human Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Interplay Between Aging and Glial Cell Dysfunction: Implications for CNS Health.Life (Basel, Switzerland) · 2025Review
- Sex-Specific Differential DNA Methylation in Mild Cognitive Impairment and Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- Brain-penetrant histone deacetylase inhibitor RG2833 improves spatial memory in females of an Alzheimer's disease rat model.Journal of Alzheimer's disease : JAD · 2025Article
- Review
- APOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia.Annals of clinical and translational neurology · 2025Article
- EpiAge: a next-generation sequencing-basedAging · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of four brain regions (temporal, frontal, entorhinal cortex, and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age-, and AD-associated epigenetic profiles. In one of these datasets it was also possible to distinguish 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiles. We showed that DNAm differences between males and females tend to be shared between the four brain regions, while aging differently affects cortical regions compared to cerebellum. We found that the proportion of sex-dependent probes whose methylation is modified also during aging is higher than expected, but that differences between males and females tend to be maintained, with only a few probes showing age-by-sex interaction. We did not find significant overlaps between AD- and sex-associated probes, nor disease-by-sex interaction effects. On the contrary, we found that AD-related epigenetic modifications are significantly enriched in probes whose DNAm varies with age and that there is a high concordance between the direction of changes (hyper or hypo-methylation) in aging and AD, supporting accelerated epigenetic aging in the disease. In summary, our results suggest that age-associated DNAm patterns concur to the epigenetic deregulation observed in AD, providing new insights on how advanced age enables neurodegeneration.
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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 Socratic graph.