2024
Aging-dependent loss of functional connectivity in a mouse model of Alzheimer’s disease and reversal by mGluR5 modulator
Mandino F, Shen X, Desrosiers-Grégoire G, O’Connor D, Mukherjee B, Owens A, Qu A, Onofrey J, Papademetris X, Chakravarty M, Strittmatter S, Lake E. Aging-dependent loss of functional connectivity in a mouse model of Alzheimer’s disease and reversal by mGluR5 modulator. Molecular Psychiatry 2024, 1-16. PMID: 39424929, DOI: 10.1038/s41380-024-02779-z.Peer-Reviewed Original ResearchFunctional connectivity deficitsConnectivity deficitsFunctional connectivityBrain connectivityAllosteric modulators of mGluR5Alzheimer's diseaseDefault-mode networkModulation of mGluR5Loss of functional connectivityResting-state fMRIApplication of fMRIWild-type controlsAged AD miceMouse model of Alzheimer's diseaseAD-related changesAD miceModel of Alzheimer's diseaseAssociated with synaptic damageMGluR5 modulationMonths of ageFMRI measurementsAmyloid accumulationDecreased connectivityBrain networksSilent allosteric modulators
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 curvesNeuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein
Stoner A, Fu L, Nicholson L, Zheng C, Toyonaga T, Spurrier J, Laird W, Cai Z, Strittmatter S. Neuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein. Alzheimer's Research & Therapy 2023, 15: 201. PMID: 37968719, PMCID: PMC10647125, DOI: 10.1186/s13195-023-01345-z.Peer-Reviewed Original ResearchConceptsSynapse lossDKI miceTau accumulationBrain immune activationNeural network dysfunctionPhospho-tau accumulationAccumulation of tauNeuronal genesInflammatory markersAD miceAβ levelsPrion proteinDystrophic neuritesImmune activationTau pathologyNeuronal gene expressionAmyloid-β OligomersGliotic reactionNetwork dysfunctionBehavioral deficitsSynaptic failureAD modelMemory impairmentAlzheimer's diseaseFunction of age
2022
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1q
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
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 mice
2010
Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein
Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Laurén J, Gimbel ZA, Strittmatter SM. Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein. Journal Of Neuroscience 2010, 30: 6367-6374. PMID: 20445063, PMCID: PMC3323924, DOI: 10.1523/jneurosci.0395-10.2010.Peer-Reviewed Original ResearchConceptsTransgenic miceAlzheimer's diseaseCellular prion proteinSpatial learningAD transgenic miceTransgenic AD modelTransgenic Alzheimer's micePrnp-/- miceAD-related phenotypesAmyloid-beta peptideAbeta accumulationAbeta plaquesAbeta levelsAD micePrion proteinAlzheimer's miceAxonal degenerationAPP expressionSynaptic markersHippocampal slicesDetectable impairmentEarly deathAD modelBehavioral impairmentsMemory impairment