grant
Contribution of a novel OPN-producing CD11c+ microglial subset to AD
Organization DANA-FARBER CANCER INSTLocation BOSTON, UNITED STATESPosted 1 Feb 2024Deadline 31 Dec 2028
NIHUS FederalResearch GrantFY2026(TNF)-α2aR phosphoprotein I2ar peptide3-D3-Dimensional3DAD dementiaAD modelAD pathologyAD patientsAD therapyAD treatmentAlzheimer Type DementiaAlzheimer beta-ProteinAlzheimer disease dementiaAlzheimer disease treatmentAlzheimer sclerosisAlzheimer syndromeAlzheimer treatmentAlzheimer'sAlzheimer's Amyloid beta-ProteinAlzheimer's DiseaseAlzheimer's amyloidAlzheimer's disease modelAlzheimer's disease pathologyAlzheimer's disease patientAlzheimer's disease therapyAlzheimer's pathologyAlzheimer's patientAlzheimer's therapyAlzheimers DementiaAmyloidAmyloid (Aβ) plaquesAmyloid Alzheimer's Dementia Amyloid ProteinAmyloid Beta-PeptideAmyloid PlaquesAmyloid Protein A4Amyloid SubstanceAmyloid beta-ProteinAmyloid βAmyloid β-PeptideAmyloid β-ProteinAnimal ModelAnimal Models and Related StudiesAntibody TherapyAutopsyAβBrainBrain Nervous SystemCD11cCD18CR4 ReceptorCachectinClinicalClinical Treatment MoabClosure by LigationCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive function abnormalCollaborationsComplement Receptor 4Complement Receptor Type 4CoupledDataDegenerative Neurologic DisordersDepositDepositionDevelopmentDigestionDisabled PersonsDisabled PopulationDiseaseDisease ProgressionDisease associated microgliaDisorderDisturbance in cognitionEncephalonEngineeringEngraftmentEta-1 proteinEta-1-Op proteinFoundationsGenesGeneticGoalsHandicappedHortega cellHumanITGAXITGAX geneITGB2ITGB2 geneImpaired cognitionInflammasomeInflammatoryInflammatory ResponseIntegrin alphaXbeta2Integrin αXβ2IntegrinsIntegrins Extracellular MatrixLCAMBLettersLeukocyte Adhesion Protein p150,95LigationMF17MT-bound tauMacrophage-Derived TNFMediatingMiceMice MammalsMicrogliaModelingModern ManMolecularMonoclonal AntibodiesMonocyte-Derived TNFMouse StrainsMurineMusNervous System Degenerative DiseasesNeural Degenerative DiseasesNeural degenerative DisordersNeuritesNeuritic PlaquesNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeutrophil GP150Neutrophil Glycoprotein Gp150OrganoidsPathogenicityPathologicPathologyPathway interactionsPeople with DisabilitiesPersons with DisabilitiesPhagocytosisPhenotypePrimary Senile Degenerative DementiaPrincipal InvestigatorProductionReceptor ProteinRegulationRegulatory PathwayReporterReportingSenile PlaquesTNFTNF ATNF AlphaTNF geneTNF-αTNFATNFαTREM2TREM2 geneTauopathiesTestingTherapeuticTherapeutic EffectTriggering Receptor Expressed in Myeloid Cells 2Triggering Receptor Expressed on Myeloid Cells 2Tumor Necrosis FactorTumor Necrosis Factor-alphaWritinga beta peptideabetaalzheimer modelamyloid betaamyloid beta plaqueamyloid-b plaqueamyloid-b proteinantibody based therapiesantibody treatmentantibody-based therapeuticsantibody-based treatmentaβ plaquesbeta amyloid fibrilbone sialoprotein 1bone sialoprotein Ibrain tissuecognitive dysfunctioncognitive functioncognitive losscored plaquedegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdevelopmentaldiagnostic biomarkerdiagnostic markerdifferentiation of pluripotent stem cellsdiffuse plaquedisabled individualdisabled peopleearly T-lympocyte activation-1 proteineffective therapyeffective treatmentgitter cellhiPSChuman diseasehuman iPShuman iPSChuman induced pluripotent cellhuman induced pluripotent stem cellshuman inducible pluripotent stem cellshuman inducible stem cellsimprovedindividuals with disabilitiesinduced human pluripotent stem cellsinsightmAbsmesogliamicroglial cellmicrogliocytemicrotubule bound taumicrotubule-bound taumodel of animalmonoclonal Absmouse modelmurine modelnecropsyneural inflammationneurodegenerative illnessneuroinflammationneuroinflammatoryneuropathologicneuropathologic tauneuropathologicalneuropathological tauneuropathologynew diagnosticsnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynext generation diagnosticsnovelnovel diagnosticsnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachosteopontinp150,95p150,95 Antigenp150,95 Glycoproteinpathwaypatient living with Alzheimer's diseasepatient suffering from Alzheimer's diseasepatient with Alzheimer'spatient with Alzheimer's diseasepatients with ADperivascular glial cellpluripotent stem cell differentiationpostmortempre-clinical studypreclinical studyprimary degenerative dementiaprogramsreceptorresponsescRNA sequencingscRNA-seqsecreted phosphoprotein 1senile dementia of the Alzheimer typesialoprotein 1side effectsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsoluble amyloid precursor proteintargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttautau Proteinstau associated neurodegenerationtau associated neurodegenerative processtau driven neurodegenerationtau factortau induced degenerationtau induced neurodegenerationtau mediated neurodegenerationtau neurodegenerative diseasetau neuropathologytau pathologytau pathophysiologytau proteinopathytau related neurodegenerationtau-induced pathologytauopathic neurodegenerative disordertauopathytherapeutic agent developmenttherapeutic developmenttherapeutic evaluationtherapeutic targettherapeutic testingthree dimensionaluptakeτ Proteins
Description preview
Summary
We have recently identified a small subset of CD11c+ microglia as the sole producer of OPN (Osteopontin; Spp1)
and major disease driver in the 5XFAD mouse model of Alzheimer’s Disease (AD). Our analysis of OPN-
producing CD11c+ microglia has divided Disease-Associated Microglia (DAM) that surround Aβ plaques into two
opposing subsets that…
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