ArticleMolecular psychiatry2019
Integrative approach to sporadic Alzheimer's disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau.
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Article in Molecular psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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41citing papers in PubMed, 1 pooled it
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41 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The landscape of multiscale transcriptomic networks and key regulators in Parkinson's disease.Nature communications · 2019Pooled it
- Iba1 deficiency impairs microglial synaptic remodeling and neuronal survival after axonal injury.Journal of neuroinflammation · 2026Article
- Genome-wide consensus transcriptional signatures identify synaptic pruning linking Alzheimer's disease and epilepsy.Molecular psychiatry · 2026Article
- Pathogen Antibodies and Parkinson's Disease: A Two-sample Mendelian Randomization Study.Current neurovascular research · 2026Article
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- DAP12 deletion reduces neuronal SLIT2 and demyelination and enhances brain resilience in female tauopathy mice.Molecular neurodegeneration · 2025Article
- Dysregulations of C1QA, C1QB, C1QC and C5AR1 as candidate biomarkers of vascular dementia.npj aging · 2025Article
- Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease.Molecular neurodegeneration · 2025Article
- The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration.Brain communications · 2025Review
- The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Connecting dementia risk loci to the CSF proteome identifies pathophysiological leads for dementia.Brain : a journal of neurology · 2024Article
- TYROBP/DAP12 knockout in Huntington's disease Q175 mice cell-autonomously decreases microglial expression of disease-associated genes and non-cell-autonomously mitigates astrogliosis and motor deterioration.Journal of neuroinflammation · 2024Article
- The Importance of Complement-Mediated Immune Signaling in Alzheimer's Disease Pathogenesis.International journal of molecular sciences · 2024Review
- Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice.Frontiers in aging neuroscience · 2024Article
- Complement in Human Brain Health: Potential of Dietary Food in Relation to Neurodegenerative Diseases.Foods (Basel, Switzerland) · 2023Review
- As a Potential Therapeutic Target, C1q Induces Synapse Loss Via Inflammasome-activating Apoptotic and Mitochondria Impairment Mechanisms in Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
- Effect of Aging and a Dual Orexin Receptor Antagonist on Sleep Architecture and Non-REM Oscillations Including an REM Behavior Disorder Phenotype in the PS19 Mouse Model of Tauopathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Microglial TREM2 at the Intersection of Brain Aging and Alzheimer's Disease.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2023Review
- Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Mickael AudrainDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Jean-Vianney Haure-MirandeDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-5748-9666
Minghui WangDepartment of Genetics and Genomic Sciences and Icahn Institute of Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0001-9171-4962
Soong Ho KimDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Tomas FanutzaDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Paramita ChakrabartyDepartment of Neuroscience and McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
Paul FraserTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Peter H St George-HyslopTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
Todd E GoldeDepartment of Neuroscience and McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
Robert D BlitzerDepartments of Pharmacological Sciences and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Eric E SchadtDepartment of Genetics and Genomic Sciences and Icahn Institute of Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-7892-8808
Bin ZhangDepartment of Genetics and Genomic Sciences and Icahn Institute of Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Michelle E EhrlichDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. michelle.ehrlich@mssm.edu.
Sam GandyDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. samuel.gandy@mssm.edu.
Icahn School of Medicine at Mount Sinai · USUniversity of Florida · USUniversity of Toronto · CAMount Sinai Hospital · US
Funding
VESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GROSSMAN, HILLEL · 1985 to 2019
$37.9MResearch Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carolyn Wei Zhu · 2020 to 2026
$31.0MIntegrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, MINGHUI, ZHANG, BIN · 2013 to 2022
$26.0MIntegrative Network Modeling of Cognitive Resilience to Alzheimer's DiseaseR01AG057907 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, HAROUTUNIAN, VAHRAM · 2017 to 2021
$6.3MSYSTEMATIC DRUG REPURPOSING TARGETING IMMUNE ACTIVATION NETWORKS IN ALZHEIMER'S DISEASE (AD)RF1AG059319 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, GANDY, SAMUEL E. · 2018 to 2018
$4.2MUse of iPSC systems to define roles of microglial TREM2/DAP12 and CR3/DAP12 complexes and their genetic variants in specifying risk for late onset sporadic Alzheimer's diseaseR01AG061894 · NIA · NEW YORK STEM CELL FOUNDATION · PI FOSSATI, VALENTINA, GANDY, SAMUEL E. · 2018 to 2022
$4.2MIntegrated understanding of complex viral network biology in Alzheimer's DiseaseRF1AG058469 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, GANDY, SAMUEL E. · 2019 to 2019
$4.1MTowards understanding the role of immune regulation of Apolipoprotein E function in Alzheimer's disease proteostasisR01AG055798 · NIA · UNIVERSITY OF FLORIDA · PI CHAKRABARTY, PARAMITA · 2017 to 2022
$1.9MIntegrated understanding of complex viral network biology in Alzheimer's DiseaseR56AG058469 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DUDLEY, JOEL THOMAS, EHRLICH, MICHELLE E · 2017 to 2017
$844kNIA NIH HHS P30 AG066514NIA NIH HHS P50 AG005138NIA NIH HHS R01 AG055798NIA NIH HHS R01 AG057907NIA NIH HHS R01 AG061894NIA NIH HHS R56 AG058469NIA NIH HHS RF1 AG058469NIA NIH HHS RF1 AG059319NIA NIH HHS U01 AG046170Wellcome Trust 203249/Z/16/Z
Abstract
TYROBP/DAP12 forms complexes with ectodomains of immune receptors (TREM2, SIRPβ1, CR3) associated with Alzheimer's disease (AD) and is a network hub and driver in the complement subnetwork identified by multi-scale gene network studies of postmortem human AD brain. Using transgenic or viral approaches, we characterized in mice the effects of TYROBP deficiency on the phenotypic and pathological evolution of tauopathy. Biomarkers usually associated with worsening clinical phenotype (i.e., hyperphosphorylation and increased tauopathy spreading) were unexpectedly increased in MAPT
Indexed as
Adaptor Proteins, Signal TransducingAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsAnimals, Genetically ModifiedBrainComplement C1qDisease Models, AnimalHumansMembrane ProteinsMiceMice, KnockoutMice, TransgenicMicrogliaPhenotypePhosphorylationAdaptor Proteins, Signal TransducingAmyloid beta-Protein PrecursorComplement C1qMembrane Proteinstau ProteinsTYROBP protein, humanTyrobp protein, mouse
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