grant
Astrocyte-secreted proteins as modulators of neurodegeneration in Down Syndrome and Alzheimers Disease
Organization UNIVERSITY OF VIRGINIALocation CHARLOTTESVILLE, UNITED STATESPosted 1 Jun 2023Deadline 29 Feb 2028
NIHUS FederalResearch GrantFY202621+ years oldAD dementiaAddressAdultAdult HumanAffectAgeAge of OnsetAgingAlzheimer Type DementiaAlzheimer beta-ProteinAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's Amyloid beta-ProteinAlzheimer's DiseaseAlzheimer's amyloidAlzheimer's precursor proteinAlzheimers DementiaAmentiaAmmon HornAmyloidAmyloid (Aβ) plaquesAmyloid A4 Protein PrecursorAmyloid Alzheimer's Dementia Amyloid ProteinAmyloid Beta-PeptideAmyloid PlaquesAmyloid Protein A4Amyloid Protein PrecursorAmyloid SubstanceAmyloid beta-ProteinAmyloid beta-Protein PrecursorAmyloid βAmyloid β-PeptideAmyloid β-ProteinAmyloid β-Protein PrecursorAstrocytesAstrocytusAstrogliaAutopsyAβBehavioralBiologicalBiologyBiotinBody TissuesBrainBrain Nervous SystemCaliforniaCell BodyCellsCharacteristicsChromosomal DisordersChromosome 21Chromosome Abnormality DisordersChromosome DisordersClinicalCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive function abnormalCompensationCongenital chromosomal diseaseCornu AmmonisDNA mutationDataData BasesData SetDatabasesDementiaDendritesDendritic SpinesDepositDepositionDiseaseDisease ProgressionDisorderDisturbance in cognitionDown SyndromeEncephalonEndoplasmic ReticulumErgastoplasmEventFoundationsFutureGene Copy NumberGene DosageGene ProteinsGene TranscriptionGeneralized GrowthGeneticGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGrowthHB-GAMHB-GAM-PTNHeparin-Binding Growth Factor-8Heparin-Binding Neurotrophic FactorHippocampusHumanImpaired cognitionIn VitroIndividuals with down syndromeIntellectual disabilityIntellectual functioning disabilityIntellectual limitationInvestigationInvestigatorsKO miceKnock-out MiceKnockout MiceLabelLaboratoriesLangdon Down syndromeLengthLinkLiteratureLive BirthLocationMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMediatingMemory DeficitMemory impairmentMentorsMessenger RNAMiceMice MammalsMiningModern ManMolecularMongolismMurineMusMutationNeonatalNerve DegenerationNeurite Growth-Promoting Factor 1Neuritic PlaquesNeurodevelopmental DisorderNeurological Development DisorderNeurologistNeuron DegenerationNull MouseOSF-1PathogenesisPathologicPathologyPeptide FragmentsPhenocopyPhenotypePopulationPrimary Senile Degenerative DementiaProtein DatabasesProtein Gene ProductsProtein SecretionProteinsProteomicsPublic HealthPyramidal neuronRNA ExpressionReportingResearchResearch PersonnelResearchersRoleSenile PlaquesSeriesSingle-Nucleus SequencingSpinal ColumnSpineStaining methodStainsStrepavidinStreptavidinSynapsesSynapsinsSynapticSystemTechnologyTestingTissue GrowthTissuesTrainingTranscriptTranscriptionTrisomy 21Ts65DnUniversitiesVertebral columnViralVirusVitamin HWorka beta peptideabetaabeta accumulationabeta aggregationaccelerated agingaccelerated biological ageaccelerated biological agingadulthoodage accelerationagesamyloid betaamyloid beta accumulationamyloid beta aggregationamyloid beta plaqueamyloid precursor proteinamyloid β accumulationamyloid β aggregationamyloid-b plaqueamyloid-b proteinastrocytic gliaastrogliosisaβ accumulationaβ aggregationaβ plaquesbackbonebeta amyloid fibrilbiologiccareercell typechromosome 21 trisomychromosome 21 trisomy syndromecoenzyme Rcognitive dysfunctioncognitive losscompare to controlcomparison controlconditioned fearcongenital acromicria syndromecored plaquedata basedendrite spinedensitydifferential expressiondifferentially expresseddiffuse plaquedown syndrome individualsdown syndrome patientsexperimentexperimental researchexperimental studyexperimentsfear conditioninggenome mutationheparin affin regulatory peptideheparin-binding growth-associated moleculehippocampalhippocampal pyramidal neuronin vivointellectual and developmental disabilityinterestknock-downknockdownlife-time risklifetime risklimited intellectual functioningmRNAmRNA Expressionmemory dysfunctionmorbus Downmouse Ts65Dnmouse modelmurine modelnecropsyneural degenerationneurodegenerationneurodegenerativeneurodevelopmental diseaseneurological degenerationneuronal degenerationneuropathologicneuropathologicalneuropathologynovelontogenyoverexpressoverexpressionpatients with down syndromepeople with down syndromepleiotrophinpostmortemprimary degenerative dementiapseudohypertrophic progressive muscular dystrophysNuc-Seqsenile dementia of the Alzheimer typesingle nucleus RNA-sequencingsingle nucleus seqsingle-nucleus RNA-seqsnRNA sequencingsnRNA-seqsocial rolesoluble amyloid precursor proteinspatial memorysynapsetherapeutic targettranscriptional differencestrisomy 21 syndrome
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Project Summary/Abstract
Down Syndrome (DS) is a neurodevelopmental disorder caused by trisomy of chromosome 21, and with age a
majority of DS patients develop neuropathological hallmarks associated with Alzheimer’s Disease (AD), including
amyloid plaque deposition and astrogliosis, as well as clinical dementia (cooccurrence of DS with AD is…
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