ArticleScience advances2024
Brain cell-type shifts in Alzheimer's disease, autism, and schizophrenia interrogated using methylomics and genetics.
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Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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21citing papers in PubMed, 2 pooled it
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled 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
- Genetic architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations inEpigenetics · 2024Pooled it
- Peripheral blood DNA methylation partially reports on immune cell type composition in the frontal brain.Brain, behavior, & immunity - health · 2026Article
- Single-cell profiling of DNA methylation in autism spectrum disorder prefrontal cortex reveals distinct regulatory and aging signatures.Cell genomics · 2026Article
- Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo.Nature neuroscience · 2026Article
- Captopril restores microglial homeostasis and reverses ASD-like phenotype in a model of ASD induced by exposure in utero to anti-caspr2 IgG.Molecular psychiatry · 2026Article
- Oligodendrocyte: Development, Plasticity, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- The role of low subcortical iron, white matter myelin, and oligodendrocytes in schizophrenia: a quantitative susceptibility mapping and diffusion tensor imaging study.Molecular psychiatry · 2026Article
- Microglia in autism spectrum disorder: heterogeneity, immunometabolism, and synapse-related pathways.Frontiers in immunology · 2026Review
- Epigenetics in Alzheimer's disease: from molecular mechanisms to emerging novel biomarkers.Frontiers in aging neuroscience · 2026Review
- Microglia as critical mediators linking perinatal immune stress to mental health trajectories.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Epigenetic and transcriptomic alterations precede amyloidosis in the Alzheimer's disease AppScientific reports · 2025Article
- Gene module-trait network analysis uncovers cell type specific systems and genes relevant to Alzheimer's Disease.Acta neuropathologica communications · 2025Article
- Deep learning-based cell type profiles reveal signatures of Alzheimer's disease resilience and resistance.Brain : a journal of neurology · 2025Article
- Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions.Acta pharmaceutica Sinica. B · 2025Review
- Dynamic convergence of neurodevelopmental disorder risk genes across neurodevelopment.bioRxiv : the preprint server for biology · 2025Article
- Integrating Genetic and Single-Cell Genomic Data to Reveal Brain Cell-Specific Regulation of Attention-Deficit/Hyperactivity Disorder Risk in the Prefrontal Cortex.Brain and behavior · 2025Article
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities.Communications biology · 2025Article
- Identification of Brain Cell Type-Specific Therapeutic Targets for Glioma From Genetics.CNS neuroscience & therapeutics · 2024Article
Corrections and comments
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Authors and funding
22 authors.
Chloe X YapMater Research Institute, University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0002-1788-2842
Daniel D VoDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-2057-969X
Matthew G HeffelDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Arjun BhattacharyaDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0003-1196-4385
Cindy WenDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0001-8747-8231
Yuanhao YangMater Research Institute, University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0002-5857-0124
Kathryn E KemperInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0002-9288-4522
Jian ZengInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0001-8801-5220
Zhili ZhengInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0003-2102-221X
Zhihong ZhuInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID 0000-0002-6783-3037
Eilis HannonDepartment of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK.ORCID 0000-0001-6840-072X
Dorothea Seiler VellameDepartment of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK.ORCID 0000-0002-6905-0474
Alice FranklinDepartment of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK.ORCID 0000-0001-9793-582X
Christa CaggianoBioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA.
Brie WamsleyDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-4454-9834
Daniel H GeschwindDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-2896-3450
Noah ZaitlenDepartment of Neurology, University of California Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-3553-3670
Alexander GusevDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7980-4620
Bogdan PasaniucDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jonathan MillDepartment of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK.ORCID 0000-0003-1115-3224
Chongyuan LuoDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Michael J GandalDepartment of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0001-5800-5128
Funding
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MSUPPLEMENT 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
$43.3MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MMulti-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7MPathway 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
$13.6MDiscovery of Novel Proteomic Targets in Alzheimer's DiseaseU01AG046161 · NIA · EMORY UNIVERSITY · PI BENNETT, DAVID ALAN, GESCHWIND, DANIEL H · 2014 to 2018
$8.4M Functional Genomics of Human Brain DevelopmentP50MH106934 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2014 to 2019
$7.9MCis-Regulatory Epigenome Mappings in SchizophreniaU01MH103392 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, SKLAR, PAMELA · 2014 to 2017
$7.6MMolecular Profiling of SchizophreniaR01MH110921 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHESS, ANDREW J, ROUSSOS, PANAGIOTIS · 2016 to 2020
$6.9MTranscriptional and Epigenetic Signatures of Human Brain Development and AutismU01MH103339 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD, STATE, MATTHEW W. · 2014 to 2017
$6.5M1/2 Cell Type and Region-Specific Regulatory Networks in Human Brain Development and DisordersU01MH116488 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2018 to 2022
$6.5MNIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG036042NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG048015NIA NIH HHS RC2 AG036547NIA NIH HHS RF1 AG057473NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG061356NIDA NIH HHS U01 DA048279NIMH NIH HHS P50 MH106934NIMH NIH HHS R01 MH094714NIMH NIH HHS R01 MH105472NIMH NIH HHS R01 MH105898NIMH NIH HHS R01 MH109677NIMH NIH HHS R01 MH109715NIMH NIH HHS R01 MH110905NIMH NIH HHS R01 MH110920NIMH NIH HHS R01 MH110921NIMH NIH HHS R01 MH110926NIMH NIH HHS R01 MH110927NIMH NIH HHS R01 MH110928NIMH NIH HHS R01 MH111721NIMH NIH HHS R01 MH116529NIMH NIH HHS R01 MH117291NIMH NIH HHS R01 MH117292NIMH NIH HHS R01 MH117293NIMH NIH HHS R01 MH117406NIMH NIH HHS R01 MH121521NIMH NIH HHS R01 MH123922NIMH NIH HHS R01 MH125252NIMH NIH HHS R01 MH125516NIMH NIH HHS R01 MH126393NIMH NIH HHS R01 MH126459NIMH NIH HHS R01 MH129301NIMH NIH HHS R21 MH102791NIMH NIH HHS R21 MH103877NIMH NIH HHS R21 MH105853NIMH NIH HHS R21 MH105881NIMH NIH HHS R21 MH109956NIMH NIH HHS R21 MH129817NIMH NIH HHS R56 MH114899NIMH NIH HHS R56 MH114901NIMH NIH HHS R56 MH114911NIMH NIH HHS U01 MH103339NIMH NIH HHS U01 MH103340NIMH NIH HHS U01 MH103346NIMH NIH HHS U01 MH103365NIMH NIH HHS U01 MH103392NIMH NIH HHS U01 MH116438NIMH NIH HHS U01 MH116441NIMH NIH HHS U01 MH116442NIMH NIH HHS U01 MH116487NIMH NIH HHS U01 MH116488NIMH NIH HHS U01 MH116489NIMH NIH HHS U01 MH116492NIMH NIH HHS U01 MH122509NIMH NIH HHS U01 MH122590NIMH NIH HHS U01 MH122591NIMH NIH HHS U01 MH122592NIMH NIH HHS U01 MH122678NIMH NIH HHS U01 MH122681NIMH NIH HHS U01 MH122849
Abstract
Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types-the functional unit of life-contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer's disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer's disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial cell loss contributes to Alzheimer's disease, with comparable effect size to
Indexed as
Alzheimer DiseaseAutistic DisorderBrainDNA MethylationSchizophreniaAgedAged, 80 and overEndothelial CellsEpigenomicsFemaleGenome-Wide Association StudyHumansMaleMiddle Aged
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