ArticleNeurobiology of aging2013
Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer's disease patients.
Article in Neurobiology of aging, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 218 papers, 3 of them syntheses that pooled it.
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Who cites it
218 citing papers in PubMed, 3 syntheses or guidelines pooled it, 416 citations in OpenAlex.
- A Meta-Analysis of Brain DNA Methylation Across Sex, Age, and Alzheimer's Disease Points for Accelerated Epigenetic Aging in Neurodegeneration.Frontiers in aging neuroscience · 2021Pooled it
- Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.Molecular neurobiology · 2016Pooled it
- The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review.PloS one · 2016Pooled it
- Folic Acid Supplementation Mitigates Alzheimer's Disease by Reducing Inflammation: A Randomized Controlled Trial.Mediators of inflammation · 2016Trial
- Recent Advances in Searching for DNMT Inhibitors and Their Potential Application in Treating Human Diseases.International journal of molecular sciences · 2026Review
- Integrative epigenomic landscape of Alzheimer's Disease brains reveals oligodendrocyte molecular perturbations associated with tau.Nature communications · 2026Article
- Microbial SCFAs as epigenetic mediators: fine-tuning the gut-brain axis in neurodegenerative disorders.Current research in microbial sciences · 2026Review
- Treadmill training induces sex-dependent changes in hippocampal epigenetic patterns and plaque-associated microglial morphology in aged TgF344 rats.Frontiers in neuroscience · 2026Article
- Aging of the human eye lens: Epigenetic landscape and therapeutic targets in age‑related cataracts (Review).International journal of molecular medicine · 2025Review
- 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
- Brain DNA Methylation Atlas of AppAging cell · 2025Article
- Direct Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution Unravels Their Distinct Roles in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Impaired Synaptic Plasticity Mechanisms in Alzheimer's Disease.Metabolic brain disease · 2025Review
- Fasting is required for many of the benefits of calorie restriction in the 3xTg mouse model of Alzheimer's disease.Nature communications · 2025Article
- The Role of Methylation in Neurodegenerative Diseases: Insights From a Bibliometric Study.Brain and behavior · 2025Article
- Homeostatic DNMT3a Activity Is Required to Restore Cognition and Hippocampal DNA Methylation in the 5xFAD Model of Alzheimer's Disease.Aging and disease · 2025Article
- Review
- Brain 5-hydroxymethylcytosine alterations are associated with Alzheimer's disease neuropathology.Nature communications · 2025Article
- Hippocampal gene expression changes associated with sequential behavioral training in a temporal lobe epilepsy rat model.Epilepsy & behavior reports · 2025Article
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
158 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Epigenetic dysregulation of gene expression is thought to be critically involved in the pathophysiology of Alzheimer's disease (AD). Recent studies indicate that DNA methylation and DNA hydroxymethylation are 2 important epigenetic mechanisms that regulate gene expression in the aging brain. However, very little is known about the levels of markers of DNA methylation and hydroxymethylation in the brains of patients with AD, the cell-type specificity of putative AD-related alterations in these markers, as well as the link between epigenetic alterations and the gross pathology of AD. The present quantitative immunohistochemical study investigated the levels of the 2 most important markers of DNA methylation and hydroxymethylation, that is, 5-methylcytidine (5-mC) and 5-hydroxymethylcytidine (5-hmC), in the hippocampus of AD patients (n = 10) and compared these to non-demented, age-matched controls (n = 10). In addition, the levels of 5-hmC in the hippocampus of a pair of monozygotic twins discordant for AD were assessed. The levels of 5-mC and 5-hmC were furthermore analyzed in a cell-type and hippocampal subregion-specific manner, and were correlated with amyloid plaque load and neurofibrillary tangle load. The results showed robust decreases in the hippocampal levels of 5-mC and 5-hmC in AD patients (19.6% and 20.2%, respectively). Similar results were obtained for the twin with AD when compared to the non-demented co-twin. Moreover, levels of 5-mC as well as the levels of 5-hmC showed a significant negative correlation with amyloid plaque load in the hippocampus (r(p) = -0.539, p = 0.021 for 5-mC and r(p) = -0.558, p = 0.016 for 5-hmC). These human postmortem results thus strengthen the notion that AD is associated with alterations in DNA methylation and hydroxymethylation, and provide a basis for further epigenetic studies identifying the exact genetic loci with aberrant epigenetic signatures.
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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.