grant
Mapping and modeling inhibitory interneurons in Alzheimer's disease and related dementias: novel strategies to reverse neural network dysfunction
Organization UNIVERSITY OF MICHIGAN AT ANN ARBORLocation ANN ARBOR, UNITED STATESPosted 15 Aug 2024Deadline 31 May 2029
NIHUS FederalResearch GrantFY2025AD dementiaAD pathologyAD related dementiaADRDAbeta clearanceAddressAffectAgeAlzheimer Type DementiaAlzheimer beta-ProteinAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's Amyloid beta-ProteinAlzheimer's DiseaseAlzheimer's amyloidAlzheimer's and related dementiasAlzheimer's brainAlzheimer's dementia and related dementiaAlzheimer's dementia or related dementiaAlzheimer's disease and related dementiaAlzheimer's disease and related disordersAlzheimer's disease brainAlzheimer's disease or a related dementiaAlzheimer's disease or a related disorderAlzheimer's disease or related dementiaAlzheimer's disease pathologyAlzheimer's disease related dementiaAlzheimer's disease therapyAlzheimer's pathologyAlzheimer's therapyAlzheimers DementiaAmentiaAmmon HornAmyloid Alzheimer's Dementia Amyloid ProteinAmyloid Beta-PeptideAmyloid Protein A4Amyloid beta-ProteinAmyloid βAmyloid β clearanceAmyloid β toxicityAmyloid β-PeptideAmyloid β-ProteinAnatomic SitesAnatomic structuresAnatomyAssayAutopsyAβAβ clearanceBasal Transcription FactorBasal transcription factor genesBehaviorBioassayBioenergeticsBiological AssayBiologyBrainBrain Nervous SystemCatalogsCell Communication and SignalingCell SignalingCell TherapyCognitionCognitiveCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive function abnormalConnector NeuronCornu AmmonisCorpus CallosumCorpus CallosumsDataDementiaDevelopment PlansDevelopment and ResearchDiseaseDisorderDisturbance in cognitionDysfunctionEEGElectroencephalogramElectroencephalographyEncephalonExhibitsFimbria of hippocampusFornix FimbriaFoundationsFunctional disorderFutureGene ExpressionGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGenesGenetic TranscriptionGoalsGraft SurvivalHippocampusHumanHyperactivityIGF-1IGF-IIGF-I-SmCImmunohistochemistryImmunohistochemistry Cell/TissueImmunohistochemistry Staining MethodImpaired cognitionImpairmentIn VitroIndividualInnovative TherapyInsulin-Like Growth Factor 1Insulin-Like Growth Factor IInsulin-Like Somatomedin Peptide IIntercalary NeuronIntercalated NeuronsIntermediary MetabolismInterneuronsInternuncial CellInternuncial NeuronIntracellular Communication and SignalingKnowledgeLearningLentiviral VectorLentivirus VectorLifeLinkLiteratureMapsMeasuresMediatorMemoryMemory DeficitMemory impairmentMentorsMetabolicMetabolic ProcessesMetabolismMethodsMissionMitochondriaModelingModern ManMorphologyNational Institutes of HealthNerve CellsNerve DegenerationNerve UnitNervous System DiseasesNervous System DisorderNeural CellNeurocyteNeurologic DisordersNeurological DisordersNeuron DegenerationNeuronsNeurosciencesNeurosurgeonOperative ProceduresOperative Surgical ProceduresOutcomeOutputOxidative PhosphorylationOxidative Phosphorylation PathwayPathogenesisPathogenicityPathologyPathway interactionsPatientsPerformancePhysiologicPhysiologicalPhysiologyPhysiopathologyPositionPositioning AttributePrimary Senile Degenerative DementiaProgenitor Cell TransplantationPublic HealthR & DR&DRNA ExpressionRegulationResearchScientistSignal TransductionSignal Transduction SystemsSignalingSomatomedin CStaining methodStainsStem Cell TransplantationStem cell transplantStructureSurgicalSurgical InterventionsSurgical ProcedureSynapsesSynapticSystemTestingTherapeuticTrainingTranscriptionTranscription Factor Proto-OncogeneTranscription factor genesTranslatingTransplantationUnited StatesUnited States National Institutes of HealthWorka beta peptidea-beta peptide clearanceabetaabeta peptide clearanceabeta toxicityaged groupaged groupsaged individualaged individualsaged peopleaged personaged personsaged populationaged populationsagesaging populationamyloid betaamyloid beta clearanceamyloid beta peptide clearanceamyloid beta toxicityamyloid-b proteinaβ toxicitybeta amyloid fibrilbiological signal transductionbrain cellcareer developmentcatalogcell based interventioncell mediated interventioncell mediated therapiescell-based therapeuticcell-based therapycellular therapeuticcellular therapycognitive dysfunctioncognitive functioncognitive losscognitive performancecostdecrease disabilitydecrease in disabilitydisability reductioneffective therapyeffective treatmentepileptiformexperienceglobal gene expressionglobal transcription profilehiPSChippocampalhuman iPShuman iPSChuman induced pluripotent cellhuman induced pluripotent stem cellshuman inducible pluripotent stem cellshuman inducible stem cellshuman modeliPSiPSCiPSCsimmunocytochemistryimprovedin vitro Modelin vivoinduced human pluripotent stem cellsinduced pluripotent cellinduced pluripotent stem cellinducible pluripotent cellinducible pluripotent stem cellinnovateinnovationinnovativelessen disabilitymemory dysfunctionmetabolic phenotypemetabotypeminimize disabilitymitigate disabilitymitochondrialmodel of humanmorris water mazemorris watermazemouse modelmurine modelnecropsynetwork dysfunctionneural circuitneural circuitryneural degenerationneural networkneuro-surgeonneurocircuitryneurodegenerationneurodegenerativeneurological degenerationneurological diseaseneuronalneuronal degenerationneuroprotectionneuroprotectiveneurotrophic factorneurotrophinneutrophinnew approachesnext generationnovelnovel approachesnovel strategiesnovel strategypathophysiologypathwaypopulation agingpostmortempreventpreventingprimary degenerative dementiaprogenitor transplantationreduction in disabilityresearch and developmentrestorationsenile dementia of the Alzheimer typesexslow disabilitysoluble amyloid precursor proteinspatial RNA sequencingspatial gene expression analysisspatial gene expression profilingspatial resolved transcriptome sequencingspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatially resolved transcriptomicsspatio transcriptomicsstem and progenitor cell transplantationssubstantia albasurgerysynapsesynapse formationsynaptic circuitsynaptic circuitrysynaptogenesistherapeutic targettranscription factortranscriptometranslational studytransplantwhite matter
Description preview
ABSTRACT
Alzheimer’s disease (AD) and AD-related dementias (ADRD) are prevalent and costly, with no
disease-modifying therapies. Emerging data demonstrate that disruptions within inhibitory
interneurons contribute significantly to AD/ADRD pathophysiology. Interneurons normally
regulate excitatory firing of neuronal networks, enabling the tuning…
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