ArticleNature medicine2019
Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia.
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Article in Nature medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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83citing papers in PubMed
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Who cites it
83 citing papers in PubMed, 152 citations in OpenAlex.
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- Integrated multi-omics profiling reveals novel molecular biomarkers and pathways associated with Fragile X-associated tremor/ataxia syndrome.Frontiers in molecular neuroscience · 2026Article
- A spatially informed matrix normal model for gene co-expression analysis in spatial transcriptomics studies.Nucleic acids research · 2025Article
- Olfactory-Guided Behavior Uncovers Imaging and Molecular Signatures of Alzheimer's Disease Risk.Brain sciences · 2025Article
- Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924.Scientific reports · 2025Article
- Smelling the Risk: Early Olfactory Deficits, Brain Networks, and Blood Markers of Alzheimer's Disease Risk in Humanized APOE Mice.bioRxiv : the preprint server for biology · 2025Article
- A role for astrocytic miR-129-5p in frontotemporal dementia.Translational psychiatry · 2025Article
- Exploring the Role of microRNAs as Blood Biomarkers in Alzheimer's Disease and Frontotemporal Dementia.International journal of molecular sciences · 2025Review
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- Multisensory gamma stimulation enhances adult neurogenesis and improves cognitive function in male mice with Down Syndrome.PloS one · 2025Article
- Predicting Alzheimer's disease subtypes and understanding their molecular characteristics in living patients with transcriptomic trajectory profiling.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease.Nature genetics · 2024Article
- Cross-disorder and disease-specific pathways in dementia revealed by single-cell genomics.Cell · 2024Article
- Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy.Molecular neurodegeneration · 2024Article
- Systems Genetics Analyses Reveals Key Genes Related to Behavioral Traits in the Striatum of CFW Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Plasma miR-203a-3p as a Novel Predictor of Dementia in Patients with Parkinson's Disease.International journal of molecular sciences · 2024Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 20 institutions in 13 countries.
Vivek Swarup *Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-3762-2746
Flora I Hinz *Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jessica E RexachProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Ken-Ichi NoguchiCNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.
Hiroyoshi ToyoshibaCNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.
Akira OdaCNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.
Keisuke HiraiCNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.
Arjun SarkarProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Nicholas T SeyfriedDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Chialin ChengChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stephen J HaggartyChemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
International Frontotemporal Dementia Genomics Consortium
Murray GrossmanCenter for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Vivianna M Van DeerlinThe Penn FTD Center, Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-7400-9097
John Q TrojanowskiThe Penn FTD Center, Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
James J LahAlzheimer's Disease Research Center and Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Allan I LeveyAlzheimer's Disease Research Center and Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Shinichi KondouCNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.
Daniel H GeschwindProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. dhg@mednet.ucla.edu.ORCID http://orcid.org/0000-0003-2896-3450
Neuroscience Research Australia · AUSalford Royal NHS Foundation Trust · GBNewcastle Hospitals - Campus for Ageing and Vitality · GBUniversity of Pennsylvania · USMayo Clinic · USTakeda (Japan) · JPUniversity College London · GBUniversity of California, Los Angeles · USJacksonville College · USSaarland University · DEUniversité de Lille · FRUniversity of California, San Francisco · USUniversity of Florence · ITUniversity of Manchester · GBUniversity of Milan · ITCentro San Giovanni di Dio Fatebenefratelli · ITEmory University · USErasmus University Rotterdam · NLFondazione IRCCS Istituto Neurologico Carlo Besta · ITFundació ACE · ES
Funding
Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5MTDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1MSUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6MTransgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3MTHE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9MUPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1MResearch Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI GONZALEZ HERNANDEZ, GRACIELA · 2001 to 2020
$32.5MIntegrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, PETERS, METTE · 2013 to 2022
$24.6MTRANSGENIC MODELING OF TAUOPATHYP01AG017216 · NIA · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 1999 to 2011
$12.0MDiscovery of Novel Proteomic Targets in Alzheimer's DiseaseU01AG046161 · NIA · EMORY UNIVERSITY · PI BENNETT, DAVID ALAN, GESCHWIND, DANIEL H · 2014 to 2018
$8.4MMedical Research Council G0301152Medical Research Council G0400074Medical Research Council G0502157Medical Research Council G0900652Medical Research Council G1100540Medical Research Council MC_G1000734Medical Research Council MC_U105597119Medical Research Council MC_U123192748Medical Research Council MC_UU_00005/12Medical Research Council MC_UU_00024/1Medical Research Council MC_UU_00024/7Medical Research Council MR/J009482/1Medical Research Council MR/N012453/1NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG017216NIA NIH HHS P01 AG017586NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG019610NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG032990NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046161NINDS NIH HHS R01 NS080820NINDS NIH HHS R25 NS065723NINDS NIH HHS U24 NS072026Wellcome Trust 203249/Z/16/Z
Abstract
Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. We bridge the species divide via integration with proteomic and transcriptomic data from the human brain to identify evolutionarily conserved, disease-relevant networks. We find that overexpression of miR-203, a hub of a putative regulatory microRNA (miRNA) module, recapitulates mRNA coexpression patterns associated with disease state and induces neuronal cell death, establishing this miRNA as a regulator of neurodegeneration. Using a database of drug-mediated gene expression changes, we identify small molecules that can normalize the disease-associated modules and validate this experimentally. Our results highlight the utility of an integrative, cross-species network approach to drug discovery.
Indexed as
Evolution, MolecularGene Regulatory NetworksAnimalsCell DeathDementiaDisease Models, AnimalFrontotemporal DementiaGene Expression RegulationGenetic Predisposition to DiseaseGenetic VectorsHumansMice, Inbred C57BLMice, TransgenicMicroRNAsNeurodegenerative DiseasesProteomicsMicroRNAsRNA, Messengertau Proteins
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