ArticleNature neuroscience2014
Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci.
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Article in Nature neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 582 papers, 8 of them syntheses that pooled it.
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582citing papers in PubMed, 8 pooled it
33.7field-weighted citation impact, top 1% of its field
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Who cites it
582 citing papers in PubMed, 8 syntheses or guidelines pooled it, 992 citations in OpenAlex.
- Interrogating DNA methylation associated with Lewy body pathology in a cross brain-region and multi-cohort study.Nature communications · 2026Pooled it
- 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
- Pooled it
- Genetic architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations inEpigenetics · 2024Pooled it
- MicroRNAs signatures as potential molecular markers in mild cognitive impairment: a meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer's disease.Alzheimer's research & therapy · 2023Pooled it
- Direct Conversion of Fibroblast into Neurons for Alzheimer's Disease Research: A Systematic Review.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Epigenetic changes associated with the progression of prion disease in Syrian hamsters (Prion · 2026Article
- Brain DNA methylation, APOE genotype and Alzheimer's disease neuropathology in a large postmortem cohort.Nature aging · 2026Article
- Protocol for genome-wide differential methylation using long-read DNA sequencing in the cortex of a mouse model of Alzheimer's disease.STAR protocols · 2026Article
- Early oligodendrocyte dysfunction signature in Alzheimer's disease: Insights from DNA methylomics and transcriptomics.Molecular psychiatry · 2026Article
- Differential DNA methylation in blood as potential mediator of the association between ambient PMMolecular psychiatry · 2026Article
- Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer's disease.Nature communications · 2026Article
- Genetic and pathway complexity in Alzheimer's disease: Insights from multi-omic data about the immune response and mitochondrial function.Neural regeneration research · 2026Article
- Article
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- A scalable approach to investigating sequence-to-function predictions from personal genomes.Nature methods · 2026Article
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- Associations of stable psychological traits with multi-omic subtypes of Alzheimer's dementia.Translational psychiatry · 2026Article
522 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 8 institutions in 3 countries.
Philip L De Jager1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
Gyan Srivastava1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
Katie Lunnon1] University of Exeter Medical School, University of Exeter, Exeter, UK. [2] Institute of Psychiatry, King's College London, London, UK.
Jeremy Burgess1] Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA. [2] Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Leonard C Schalkwyk1] University of Exeter Medical School, University of Exeter, Exeter, UK. [2] Institute of Psychiatry, King's College London, London, UK.ORCID 0000000170305756
Lei YuRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Matthew L Eaton1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. [2] Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Brendan T Keenan1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
Jason Ernst1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. [2] Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Cristin McCabeProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
Anna TangProgram in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Towfique Raj1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
Joseph Replogle1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
Wendy BrodeurGenetic Analysis Platform, Broad Institute, Cambridge, Massachusetts, USA.
Stacey GabrielGenetic Analysis Platform, Broad Institute, Cambridge, Massachusetts, USA.
High S Chai1] Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA. [2] Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Curtis YounkinDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Steven G YounkinDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Fanggeng ZouDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Moshe SzyfDepartment of Pharmacology and Therapeutics, McGill University, Montreal, Québec, Canada.
Charles B EpsteinEpigenomics Program, Broad Institute, Cambridge, Massachusetts, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Bradley E Bernstein1] Harvard Medical School, Boston, Massachusetts, USA. [2] Epigenomics Program, Broad Institute, Cambridge, Massachusetts, USA. [3] Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Alex Meissner1] Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Epigenomics Program, Broad Institute, Cambridge, Massachusetts, USA. [3] Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.
Nilufer Ertekin-Taner1] Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA. [2] Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Lori B Chibnik1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
Manolis Kellis1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. [2] Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Jonathan Mill1] University of Exeter Medical School, University of Exeter, Exeter, UK. [2] Institute of Psychiatry, King's College London, London, UK.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Broad Institute · USJacksonville College · USBrigham and Women's Hospital · USRush University Medical Center · USUniversity of Exeter · GBHarvard University · USKing's College London · GBMcGill University · CA
Funding
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MTHE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9MIntegrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MProduction sequencing of reference human epigenomesU01ES017155 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERNSTEIN, BRADLEY EVAN, MEISSNER, ALEXANDER · 2008 to 2012
$15.4MMayo Clinic Center for Translational Science ActivitiesKL2RR024151 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 2006 to 2011
$15.3MPathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6MRisk Factors, Pathology, and Clinical Expressions of ADRF1AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2014 to 2014
$6.0MExploring the Role of the Brain Epigenome: Cognitive Decline and Life ExperiencesRF1AG036042 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2016 to 2016
$5.5MExploring the Role of the Brain Epigenome: Cognitive Decline and Life ExperiencesR01AG036042 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2009 to 2013
$4.1MRegulatory Morif Discovery in the Human Genome Using Comparative GenomicsR01HG004037 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS · 2007 to 2015
$3.9MNCRR NIH HHS KL2 RR024151NHGRI NIH HHS R01 HG004037NIA NIH HHS AG036039NIA NIH HHS K25 AG041906NIA NIH HHS K25 AG041906-01NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG10161NIA NIH HHS P50 AG016574NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG036039NIA NIH HHS R01 AG036042NIA NIH HHS R01 AG036836NIA NIH HHS R01AG036836NIA NIH HHS R01 AG15819NIA NIH HHS R01 AG17917NIA NIH HHS R01 AG18023NIA NIH HHS RC2 AG036547NIA NIH HHS RF1 AG015819NIA NIH HHS RF1 AG036042NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIEHS NIH HHS U01 ES017155NINDS NIH HHS R01 NS080820
Abstract
We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network.
Indexed as
Adaptor Proteins, Signal TransducingAgedAged, 80 and overAlzheimer DiseaseAmyloidosisAnkyrinsBrainCarrier ProteinsCpG IslandsDNA MethylationFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIntracellular Signaling Peptides and ProteinsMaleAdaptor Proteins, Signal TransducingANK1 protein, humanAnkyrinsBIN1 protein, humanCarrier ProteinsIntracellular Signaling Peptides and ProteinsNuclear ProteinsRHBDF2 protein, humanTumor Suppressor Proteins
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