SynthesisActa neuropathologica communications2021
Sex-specific DNA methylation differences in Alzheimer's disease pathology.
Synthesis in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis 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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Distinct sex-specific DNA methylation differences in Alzheimer's disease.Alzheimer's research & therapy · 2022Pooled it
- Blood DNA Methylation Predicts Long-Term Risk of Dementia in Prospective Cohorts.medRxiv : the preprint server for health sciences · 2026Article
- PTPRN2 hypomethylation and PHB2-associated miR-153-3p maturation define dual epigenetic features linked to symptom variability in Myalgic encephalomyelitis.Journal of translational medicine · 2026Article
- Integrative epigenomic landscape of Alzheimer's Disease brains reveals oligodendrocyte molecular perturbations associated with tau.Nature communications · 2026Article
- Epigenetics in Alzheimer's disease: from molecular mechanisms to emerging novel biomarkers.Frontiers in aging neuroscience · 2026Review
- TMEM39A acts as a novel profibrotic factor to activate hepatic stellate cells partially via the cell adhesion molecule signaling axis.Frontiers in cell and developmental biology · 2026Article
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Exploring causal relationships between epigenetic age acceleration and Alzheimer's disease: a bidirectional Mendelian randomization study.Clinical epigenetics · 2025Article
- Sex Differences in Mortality and Health Care Utilization After Dementia Diagnosis.JAMA neurology · 2025Article
- Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis.iScience · 2025Article
- Identification and replication of sex-dimorphic protein quantitative trait loci across multiple ancestries and their associations with diseases.Scientific reports · 2025Article
- A comprehensive guide to genomeZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Leveraging multiomic approaches to elucidate mechanisms of heterogeneity in Alzheimer's disease: Neuropsychiatric symptoms, co-pathologies, and sex differences.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Epigenome-wide association study of cerebrospinal fluid-based biomarkers of Alzheimer's disease in cognitively normal individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 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
- Advancing Personalized Medicine in Alzheimer's Disease: Liquid Biopsy Epigenomics UnveilInternational journal of molecular sciences · 2025Article
- Blood DNA methylation signature for incident dementia: Evidence from longitudinal cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats.Biology of sex differences · 2025Article
- Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Sex is an important factor that contributes to the clinical and biological heterogeneities in Alzheimer's disease (AD), but the regulatory mechanisms underlying sex disparity in AD are still not well understood. DNA methylation is an important epigenetic modification that regulates gene transcription and is known to be involved in AD. We performed the first large-scale sex-specific meta-analysis of DNA methylation differences in AD neuropathology, by re-analyzing four recent epigenome-wide association studies totaling more than 1000 postmortem prefrontal cortex brain samples using a uniform analytical pipeline. For each cohort, we employed two complementary analytical strategies, a sex-stratified analysis that examined methylation-Braak stage associations in male and female samples separately, and a sex-by-Braak stage interaction analysis that compared the magnitude of these associations between different sexes. Our analysis uncovered 14 novel CpGs, mapped to genes such as TMEM39A and TNXB that are associated with the AD Braak stage in a sex-specific manner. TMEM39A is known to be involved in inflammation, dysregulated type I interferon responses, and other immune processes. TNXB encodes tenascin proteins, which are extracellular matrix glycoproteins demonstrated to modulate synaptic plasticity in the brain. Moreover, for many previously implicated genes in AD neuropathology, such as MBP and AZU1, our analysis provided the new insights that they were predominately driven by effects in only one sex. These sex-specific DNA methylation differences were enriched in divergent biological processes such as integrin activation in females and complement activation in males. Our study implicated multiple new loci and biological processes that affected AD neuropathology in a sex-specific manner.
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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 OpenQuestion graph.