ArticleJournal of Alzheimer's disease : JAD2012
Genome-wide DNA methylation differences between late-onset Alzheimer's disease and cognitively normal controls in human frontal cortex.
Article in Journal of Alzheimer's disease : JAD, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 5 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
134 citing papers in PubMed, 5 syntheses or guidelines pooled it, 258 citations in OpenAlex.
- Guidelines for pre-analytical conditions for assessing the methylation of circulating cell-free DNA.Clinical epigenetics · 2021Pooled it
- Sex-specific DNA methylation differences in Alzheimer's disease pathology.Acta neuropathologica communications · 2021Pooled it
- Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer's disease.Nature communications · 2020Pooled 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
- Epigenetic changes in the progression of Alzheimer's disease.Mechanisms of ageing and development · 2013Trial
- Differential DNA methylation in blood as potential mediator of the association between ambient PMMolecular psychiatry · 2026Article
- TMEM59 regulates microglial Aβ phagocytosis in a TREM2-dependent manner and acts as a potential therapeutic target for Aβ amyloidosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- 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 Region-Specific Epigenomic Reorganization and Altered Cell States in Alzheimer's Disease.bioRxiv : the preprint server for biology · 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
- TMEM59 deficiency activates chaperone-mediated autophagy and ameliorates disease-like pathologies in tauopathy model mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes.Nature genetics · 2025Article
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- DNA Methylation in Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- Mitochondrial One-Carbon Metabolism and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Epigenetics in Alzheimer's Disease: A Critical Overview.International journal of molecular sciences · 2024Review
- Genome-Wide DNA Methylation in Early-Onset-Dementia Patients Brain Tissue and Lymphoblastoid Cell Lines.International journal of molecular sciences · 2024Article
- Review
- ISGylation of DRP1 closely balances other post-translational modifications to mediate mitochondrial fission.Cell death & disease · 2024Article
74 more citing papers are in PubMed but not listed here.
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 1 institution in 1 country.
Funding
Abstract
Evidence supports a role for epigenetic mechanisms in the pathogenesis of late-onset Alzheimer's disease (LOAD), but little has been done on a genome-wide scale to identify potential sites involved in disease. This study investigates human postmortem frontal cortex genome-wide DNA methylation profiles between 12 LOAD and 12 cognitively normal age- and gender-matched subjects. Quantitative DNA methylation is determined at 27,578 CpG sites spanning 14,475 genes via the Illumina Infinium HumanMethylation27 BeadArray. Data are analyzed using parallel linear models adjusting for age and gender with empirical Bayes standard error methods. Gene-specific technical and functional validation is performed on an additional 13 matched pair samples, encompassing a wider age range. Analysis reveals 948 CpG sites representing 918 unique genes as potentially associated with LOAD disease status pending confirmation in additional study populations. Across these 948 sites the subtle mean methylation difference between cases and controls is 2.9%. The CpG site with a minimum false discovery rate located in the promoter of the gene Transmembrane Protein 59 (TMEM59) is 7.3% hypomethylated in cases. Methylation at this site is functionally associated with tissue RNA and protein levels of the TMEM59 gene product. The TMEM59 gene identified from our discovery approach was recently implicated in amyloid-β protein precursor post-translational processing, supporting a role for epigenetic change in LOAD pathology. This study demonstrates widespread, modest discordant DNA methylation in LOAD-diseased tissue independent from DNA methylation changes with age. Identification of epigenetic biomarkers of LOAD risk may allow for the development of novel diagnostic and therapeutic targets.
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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.