grant
Targeted lipid-siRNA complexes for SPP1-silencing in Alzheimer's Disease
Organization VANDERBILT UNIVERSITYLocation Nashville, UNITED STATESPosted 1 Sept 2025Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025(TNF)-α2aR phosphoprotein I2ar peptideAD dementiaAD modelAD pathologyAddressAdventitial CellAgeAlzheimer Type DementiaAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's DiseaseAlzheimer's disease modelAlzheimer's disease pathologyAlzheimer's pathologyAlzheimers DementiaAmentiaAmyloidAmyloid (Aβ) plaquesAmyloid PlaquesAmyloid SubstanceAstrocytesAstrocytusAstrogliaAβ burdenBlood SerumBlood VesselsBlood capillariesBrainBrain Nervous SystemCachectinCell BodyCellsCerebrospinal FluidCessation of lifeCharacteristicsChemistryCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive function abnormalComplexD-MannoseDataDeathDementiaDevelopmentDiffusionDiseaseDisease ProgressionDisorderDisturbance in cognitionDoseELISAEncephalonEndothelial CellsEngineeringEnzyme-Linked Immunosorbent AssayEta-1 proteinEta-1-Op proteinFibroblastsFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryGene InactivationGene SilencingGenesGoalsHortega cellImmuneImmunesImmunohistochemistryImmunohistochemistry Cell/TissueImmunohistochemistry Staining MethodImpaired cognitionIn VitroIndividualInflammatoryInjectionsInvestigationKnock-outKnockoutLabelLaboratoriesLigandsLipidsMacrophageMacrophage-Derived TNFMannopyranoseMannopyranosideMannoseMeasuresMediatingMemory LossMicrogliaMonocyte-Derived TNFMφNeuritic PlaquesOnset of illnessPathogenesisPathogenicityPericapillary CellPericytesPerivascular CellPrimary Senile Degenerative DementiaProcessProteinsReceptor ProteinResearchRisk FactorsRoleRouget CellsSenile PlaquesSeriesSerumShort interfering RNASmall Interfering RNASourceSpecificityStaining methodStainsTNFTNF ATNF AlphaTNF geneTNF-αTNFATNFαTechnologyTherapeutic InterventionThioflavin STimeTranscriptTumor Necrosis FactorTumor Necrosis Factor-alphaWorka-beta burdenabeta burdenage associatedage associated neurodegenerationage associated neurodegenerative diseaseage associated neurodegenerative disorderage correlatedage dependentage dependent neurodegenerationage dependent neurodegenerative conditionage dependent neurodegenerative diseaseage dependent neurodegenerative disorderage linkedage relatedage related neurodegenerationage specificage-driven neurodegenerative disordersage-related neurodegenerative diseaseage-related neurodegenerative disorderagesaging associated neurodegenerationaging associated neurodegenerative diseaseaging related neurodegenerationaging related neurodegenerative diseaseaging related neurodegenerative disorderalzheimer modelamyloid beta plaqueamyloid burdenamyloid pathologyamyloid-b plaqueastrocytic gliaaβ plaquesbeta amyloid burdenbone sialoprotein 1bone sialoprotein Ibrain vascular damagebrain vascular lesioncapillarycell typecerebral spinal fluidcerebral vascular damagecerebrovascular damagecerebrovascular lesioncognitive dysfunctioncognitive losscored plaquecytokinedeliver short interfering RNAdeliver siRNAdeliver small interfering RNAdelivery system for siRNAdelivery system for small interfering RNAdelivery vectors for siRNAdesigndesigningdevelopmentaldifferential expressiondifferentially expresseddiffuse plaquediffuseddiffusesdiffusingdiffusionsdisabilitydisease onsetdisorder onsetearly T-lympocyte activation-1 proteinenzyme linked immunoassayflow cytophotometryfluorophoregitter cellimprovedin vivoinsightintervention therapyknock-downknockdownmannose receptormemory declinemesogliamicroglial cellmicrogliocytemouse modelmurine modelneural inflammationneuroinflammationneuroinflammatoryneurotoxicnew approachesnovelnovel approachesnovel strategiesnovel strategyosteopontinperivascular glial cellprimary degenerative dementiareceptorsecreted phosphoprotein 1senile dementia of the Alzheimer typeshort interfering RNA deliverysiRNAsiRNA deliverysialoprotein 1small interfering RNA deliverysocial rolespinal fluidtargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic outcometherapeutically effectivetherapy outcometooltranscriptional differencestranscriptional silencinguptakevascularβ-amyloid burdenβamyloid burden
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Project Summary:
Alzheimer's Disease (AD) is a fatal neurodegenera�ve disorder characterized by progressive memory loss and
execu�ve dysfunc�on. Recent research has highlighted the cri�cal role of inflamma�on in AD pathogenesis, with
secreted phosphoprotein 1 (SPP1) iden�fied as a key driver of neuroinflamma�on. SPP1 levels are increased in
both the…
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