2023
PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease
Zheng C, Nicholson L, Chen B, Toyonaga T, Liu M, Strittmatter S, Carson R, Huang Y, Cai Z. PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.081695.Peer-Reviewed Original ResearchAPP/PS1 micePS1 miceWT miceCentral nervous systemTime-activity curvesAlzheimer's diseaseAPP/PS1 transgenic miceAPP/PS1 transgenic AD miceMouse brainAge-matched WT controlsPS1 transgenic miceAPP/PS1Transgenic AD miceDynamic PET imaging dataROCK2 protein expressionAD drug discoveryHigh tracer uptakeMin post injectionPET imaging resultsExpression levelsReference tissue model 2PET imaging dataProtein expression levelsAD miceRegional time-activity curvesDecreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16
Zheng C, Toyonaga T, Chen B, Nicholson L, Mennie W, Liu M, Spurrier J, Deluca K, Strittmatter S, Carson R, Huang Y, Cai Z. Decreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16. Frontiers In Neurology 2023, 14: 1045644. PMID: 36846134, PMCID: PMC9945093, DOI: 10.3389/fneur.2023.1045644.Peer-Reviewed Original ResearchStandardized uptake value ratioDistribution volume ratioAlzheimer's diseaseSimplified reference tissue modelSynapse lossMouse modelAPP/PS1 miceAge-matched wild-type miceAPPswe/PS1dE9 mouse modelAPP/PS1 AD mouse modelSlow brain kineticsAD mouse modelSynaptic vesicle glycoprotein 2APseudo-reference regionWild-type miceUptake value ratioMonths of ageDifferent brain regionsDifferent imaging windowsFamilial Alzheimer's diseasePET imaging studiesReference tissue modelPS1 miceBrain stemBrain kinetics
2020
Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging
Sadasivam P, Fang XT, Toyonaga T, Lee S, Xu Y, Zheng MQ, Spurrier J, Huang Y, Strittmatter SM, Carson RE, Cai Z. Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging. Molecular Imaging And Biology 2020, 23: 372-381. PMID: 33258040, PMCID: PMC8105262, DOI: 10.1007/s11307-020-01567-9.Peer-Reviewed Original ResearchConceptsBrain stemAlzheimer's diseaseMin postinjectionAnimal modelsAPP/PS1 miceReference regionStandardized uptake value ratioDynamic PET imaging dataUptake value ratioRodent brain tissueStatic PET scansDifferent imaging windowsPET imaging dataWild-type controlsReference tissue modelPS1 miceAD pathogenesisTherapeutic effectMouse modelRodent modelsLittermate controlsPET scansRodent brainPreclinical imaging studiesTherapeutic drug efficacy
2019
In Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease
Toyonaga T, Smith LM, Finnema SJ, Gallezot JD, Naganawa M, Bini J, Mulnix T, Cai Z, Ropchan J, Huang Y, Strittmatter SM, Carson RE. In Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease. Journal Of Nuclear Medicine 2019, 60: 1780-1786. PMID: 31101744, PMCID: PMC6894376, DOI: 10.2967/jnumed.118.223867.Peer-Reviewed Original ResearchConceptsAPP/PS1 micePS1 miceAlzheimer's diseaseWT miceSynaptic densityC-UCBDrug washoutTreatment effectsPresenilin 1 (PS1) double transgenic miceHippocampal synaptic densityAPP/PS1Double transgenic miceEnd of treatmentWild-type miceAmyloid precursor proteinEarly Alzheimer's diseaseSignificant differencesSUVR-1New PET tracersMild cognitive impairmentAD miceSynaptic deficitsOral gavageAD treatmentHealthy subjects
2017
Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network
Takahashi H, Klein ZA, Bhagat SM, Kaufman AC, Kostylev MA, Ikezu T, Strittmatter SM, For the Alzheimer’s Disease Neuroimaging Initiative. Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. Acta Neuropathologica 2017, 133: 785-807. PMID: 28070672, PMCID: PMC5391267, DOI: 10.1007/s00401-017-1668-z.Peer-Reviewed Original ResearchConceptsAPP/PS1 micePS1 micePGRN deficiencyAlzheimer's diseaseAD risk variantsCerebrospinal fluid Aβ levelsLoss of progranulinMicroglial Aβ phagocytosisCSF tau levelsFrontotemporal lobar degenerationRisk variantsAPPswe/Aβ phagocytosisNeuronal injuryAβ levelsAβ pathologyCerebral amyloidosisAxonal dystrophyTau pathologyTau levelsComplement depositionPGRN levelsAD pathophysiologyAmyloid imagingProgranulin deficiency
2016
Early Activation of Experience-Independent Dendritic Spine Turnover in a Mouse Model of Alzheimer's Disease.
Heiss JK, Barrett J, Yu Z, Haas LT, Kostylev MA, Strittmatter SM. Early Activation of Experience-Independent Dendritic Spine Turnover in a Mouse Model of Alzheimer's Disease. Cerebral Cortex 2016, 27: 3660-3674. PMID: 27365298, PMCID: PMC6059166, DOI: 10.1093/cercor/bhw188.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAlzheimer DiseaseAmyloid beta-Protein PrecursorAnalysis of VarianceAnimalsCerebral CortexDendritic SpinesDisease Models, AnimalGene Expression ProfilingGreen Fluorescent ProteinsHippocampusHumansImaging, Three-DimensionalImmunoprecipitationMiceMice, Inbred C57BLMice, TransgenicMutationNeuroimagingPlaque, AmyloidPresenilin-1Prion ProteinsProto-Oncogene Proteins c-fosSensory DeprivationTime FactorsVibrissaeConceptsAPP/PS1 miceDendritic spine turnoverSpine turnoverAlzheimer's diseasePS1 miceAged APP/PS1 miceYoung APP/PS1 miceAPP/PS1 mouse brainSoluble Aβ oligomersLipid-metabolizing genesAPPswe/Synaptic lossCerebral cortexSynapse densityAβ plaquesSynaptic dysregulationLack responsivenessMouse modelDendritic spinesPersistent spinesSynapse turnoverPlaque formationMouse brainYounger ageCellular prion protein
2015
Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer’s disease mouse model
Nygaard HB, Kaufman AC, Sekine-Konno T, Huh LL, Going H, Feldman SJ, Kostylev MA, Strittmatter SM. Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer’s disease mouse model. Alzheimer's Research & Therapy 2015, 7: 25. PMID: 25945128, PMCID: PMC4419386, DOI: 10.1186/s13195-015-0110-9.Peer-Reviewed Original ResearchAPP/PS1 miceSpike-wave dischargesAD mouse modelDisease mouse modelPS1 miceAmyloid precursor proteinMouse modelMemory impairmentDisease miceEpileptiform activitySurrogate markerTransgenic Alzheimer's disease miceAlzheimer's disease mouse modelSynaptic vesicle protein 2AAberrant network activityAlzheimer's disease miceReliable surrogate markerSpatial memory impairmentTransgenic mouse modelWidespread neuronal dysfunctionSpatial memory functionTransgenic mouse strainAntiepileptic drug ethosuximideIntroductionRecent studiesAD miceFyn inhibition rescues established memory and synapse loss in Alzheimer mice
Kaufman AC, Salazar SV, Haas LT, Yang J, Kostylev MA, Jeng AT, Robinson SA, Gunther EC, van Dyck CH, Nygaard HB, Strittmatter SM. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Annals Of Neurology 2015, 77: 953-971. PMID: 25707991, PMCID: PMC4447598, DOI: 10.1002/ana.24394.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseTransgenic miceGlu receptorsAPP/PS1 transgenic miceAPP/PS1 miceMemory deficitsEffective disease-modifying agentsAD mouse modelPS1 transgenic miceAD transgenic miceDisease-modifying agentsTau transgenic miceWeeks of treatmentPrecursor protein metabolismSpatial memory deficitsNovel object recognitionMorris water mazeBrain slice assaysAZD0530 treatmentMicroglial activationPS1 miceVehicle treatmentSynapse lossAlzheimer's miceAD pathology
2013
Delayed amyloid plaque deposition and behavioral deficits in outcrossed AβPP/PS1 mice
Couch BA, Kerrisk ME, Kaufman AC, Nygaard HB, Strittmatter SM, Koleske AJ. Delayed amyloid plaque deposition and behavioral deficits in outcrossed AβPP/PS1 mice. The Journal Of Comparative Neurology 2013, 521: 1395-1408. PMID: 23047754, PMCID: PMC3562562, DOI: 10.1002/cne.23239.Peer-Reviewed Original ResearchConceptsAβPP/PS1 micePS1 micePlaque burdenPlaque depositionBehavioral deficitsRadial arm water maze performanceBehavioral impairmentsAlzheimer's diseaseAβPP processingPresenilin 1Amyloid-β precursor proteinLower plaque burdenProgressive neurodegenerative dementiaAmyloid plaque depositionAmyloid plaque accumulationAmyloid plaque burdenAD-like featuresNovel object recognitionWater maze performanceMonths of ageDendrite lossAD progressionNeurodegenerative dementiaPlaque accumulationMixed genetic background