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Interneuron dysfunction and the emergence of tau pathology in early Alzheimer’s disease
NIHUS FederalResearch GrantFY2025AD dementiaAD modelAD pathologyAccelerationAcuteAddressAdeno-Associated VirusesAffectAlzheimer Type DementiaAlzheimer beta-ProteinAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's Amyloid beta-ProteinAlzheimer's DiseaseAlzheimer's amyloidAlzheimer's disease modelAlzheimer's disease pathologyAlzheimer's disease patientAlzheimer's pathologyAlzheimer's patientAlzheimers DementiaAmentiaAmyloid (Aβ) plaquesAmyloid Alzheimer's Dementia Amyloid ProteinAmyloid Beta-PeptideAmyloid PlaquesAmyloid Protein A4Amyloid beta-ProteinAmyloid βAmyloid β-PeptideAmyloid β-ProteinAβBrain regionCognitionCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive function abnormalConnector NeuronDataDementiaDependoparvovirusDependovirusDiseaseDisorderDissectionDisturbance in cognitionDysfunctionElectrophysiologyElectrophysiology (science)EnhancersEntorhinal AreaEquilibriumEventExperimental TherapiesFunctional disorderGene ExpressionGene Expression InhibitorGenesGeneticGenetic EnhancementHumanHuman Amyloid Precursor ProteinImmunohistochemistryImmunohistochemistry Cell/TissueImmunohistochemistry Staining MethodImpaired cognitionIntercalary NeuronIntercalated NeuronsInterneuronsInternuncial CellInternuncial NeuronInterventionInvestigationInvestigational TherapiesInvestigational TreatmentsLateralLinkMT-bound tauMeasuresMemoryMiceMice MammalsModelingModern ManMolecular ConfigurationMolecular ConformationMolecular StereochemistryMurineMusNerve CellsNerve DegenerationNerve UnitNeural CellNeuritic PlaquesNeurocyteNeurofibrillary TanglesNeuron DegenerationNeuronsNeurophysiology / ElectrophysiologyParvalbuminsPathologicPathologyPhenotypePhysiologyPhysiopathologyPredispositionPrimary Senile Degenerative DementiaProcessPropertyRoleSenile PlaquesSliceSusceptibilitySystemTauopathiesTimeTransgenic OrganismsViralWild Type MouseWorka beta peptideabetaabeta accumulationabeta aggregationabnormal tauabnormally aggregated tau proteinadeno associated virus groupalzheimer modelamyloid betaamyloid beta accumulationamyloid beta aggregationamyloid beta plaqueamyloid β accumulationamyloid β aggregationamyloid-b plaqueamyloid-b proteinaβ accumulationaβ aggregationaβ plaquesbalancebalance functionbeta amyloid associated pathologybeta amyloid fibrilbeta amyloid pathologycell typecognitive dysfunctioncognitive lossconformationconformationalconformational stateconformationallyconformationscored plaquediffuse plaquedisease modeldisorder modelelectrophysiologicalentorhinal cortexexcitatory neuronexperimental therapeutic agentsexperimental therapeuticsfilamentous tau inclusiongenetic inhibitorhuman modelhyper-phosphorylated tauhyperphosphorylated tauin vivoinsightinsoluble aggregatemicrotubule associated protein tau aggregationmicrotubule associated protein tau depositmicrotubule associated protein tau mutationmicrotubule bound taumicrotubule-associated protein tau mutationmicrotubule-bound taumodel of humanmouse modelmurine modelmutantmutant taumutation in microtubule associated protein taumutation in microtubule-associated protein tauneural degenerationneurodegenerationneurodegenerativeneurofibrillary degenerationneurofibrillary lesionneurofibrillary pathologyneurological degenerationneuronalneuronal degenerationneuronal excitabilityneuropathologic tauneuropathological taupaired helical filament of taupatch clamppathogenic taupathogenic tau gene mutationpathological change in taupathophysiologypatient living with Alzheimer's diseasepatient suffering from Alzheimer's diseasepatient with Alzheimer'spatient with Alzheimer's diseasepreservationprimary degenerative dementiaprotein aggregateprotein aggregationresponseself-aggregate tausenile dementia of the Alzheimer typesocial rolesoluble amyloid precursor proteintangletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttautau PHFtau Proteinstau abnormalitytau accumulationtau aggregatetau aggregationtau associated neurodegenerationtau associated neurodegenerative processtau driven neurodegenerationtau factortau fibrillizationtau filamenttau induced degenerationtau induced neurodegenerationtau intronic mutationtau mediated neurodegenerationtau mutationtau neurodegenerative diseasetau neurofibrillary tangletau neuropathologytau oligomertau paired helical filamenttau pathological changetau pathologytau pathophysiologytau polymerizationtau proteinopathytau related neurodegenerationtau-induced pathologytau-tau interactiontauopathic neurodegenerative disordertauopathytransgenicwildtype mouseβ-amyloid pathologyτ Proteinsτ aggregationτ mutation
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PROJECT SUMMARY
Alzheimer's disease (AD) is the most common form of dementia, causing a neurodegenerative cascade,
accompanied by two hallmarks of AD pathology: the accumulation of the amyloid-beta (Aβ) and tau proteins
into amyloid plaques and neurofibrillary tau tangles. Numerous investigational therapies have been
unsuccessful at treating…
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