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 modulatorsLysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism
Takahashi H, Perez-Canamas A, Lee C, Ye H, Han X, Strittmatter S. Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism. Communications Biology 2024, 7: 1088. PMID: 39237682, PMCID: PMC11377756, DOI: 10.1038/s42003-024-06810-5.Peer-Reviewed Original ResearchConceptsMyelin lipid metabolismCo-immunoprecipitation assaysSulfated derivative sulfatideLipid metabolismAssociated with multiple neurological disordersCo-immunoprecipitationTMEM106BTransmembrane proteinsAmyloid fibrilsTMEM106B deficiencyHypomyelinating leukodystrophyAlzheimer's diseasePhysiological functionsFrontotemporal dementiaMolecular levelNeurodegenerative brainGalactosylceramidaseLipidomic analysisMultiple neurological disordersMetabolismMyelin lipidsDecreased levelsEndolysosomesAmyloidGalactosylceramidase activityWhole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease
Xicota L, Cosentino S, Vardarajan B, Mayeux R, Perls T, Andersen S, Zmuda J, Thyagarajan B, Yashin A, Wojczynski M, Krinsky‐McHale S, Handen B, Christian B, Head E, Mapstone M, Schupf N, Lee J, Barral S, Study T, Abner E, Adams P, Aguirre A, Albert M, Albin R, Allen M, Alvarez L, Andrews H, Apostolova L, Arnold S, Asthana S, Atwood C, Ayres G, Barber R, Barnes L, Barral S, Bartlett J, Beach T, Becker J, Beecham G, Benchek P, Bennett D, Bertelson J, Biber S, Bird T, Blacker D, Boeve B, Bowen J, Boxer A, Brewer J, Burke J, Burns J, Bush W, Buxbaum J, Byrd G, Cantwell L, Cao C, Carlsson C, Carrasquillo M, Chan K, Chasse S, Chen Y, Chesselet M, Chin N, Chui H, Chung J, Craft S, Crane P, Cranney M, Cruchaga C, Cuccaro M, Culhane J, Cullum C, Darby E, Davis B, De Jager P, DeCarli C, DeToledo J, Dickson D, Dobbins N, Duara R, Ertekin‐Taner N, Evans D, Faber K, Fairchild T, Fallin D, Fallon K, Fardo D, Farlow M, Farrell J, Farrer L, Fernandez‐Hernandez V, Foroud T, Frosch M, Galasko D, Gamboa A, Gauthreaux K, Gefen T, Geschwind D, Ghetti B, Gilbert J, Goate A, Grabowski T, Graff‐Radford N, Griswold A, Haines J, Hakonarson H, Hall K, Hall J, Hamilton R, Hamilton‐Nelson K, Han X, Harari O, Hardy J, Harrell L, Head E, Henderson V, Hernandez M, Honig L, Huebinger R, Huentelman M, Hulette C, Hyman B, Hynan L, Ibanez L, Jarvik G, Jayadev S, Jin L, Johnson K, Johnson L, Jones B, Jun G, Kamboh M, Kang M, Karydas A, Katz M, Kauwe J, Kaye J, Keene C, Keller B, Khaleeq A, Kim R, Knebl J, Kowall N, Kramer J, Kukull W, Kunkle B, Kuzma A, LaFerla F, Lah J, Larson E, Lerch M, Lerner A, Leung Y, Leverenz J, Levey A, Lieberman A, Lipton R, Lopez O, Lunetta K, Lyketsos C, Mains D, Manly J, Mark L, Marquez D, Marson D, Martin E, Masliah E, Massman P, Masurkar A, Mayeux R, McCormick W, McCurry S, McDonough S, McKee A, Mesulam M, Mez J, Miller B, Miller C, Mock C, Moghekar A, Montine T, Monuki E, Mooney S, Morris J, Mukherjee S, Myers A, Naj A, Nguyen T, Noble J, Nudelman K, O'Bryant S, Ormsby K, Ory M, Palmer R, Parisi J, Paulson H, Pavlik V, Paydarfar D, Perez V, Pericak‐Vance M, Petersen R, Polk M, Qu L, Quiceno M, Quinn J, Raj A, Rajabli F, Ramanan V, Reiman E, Reisch J, Reitz C, Ringman J, Roberson E, Rodriguear M, Rogaeva E, Rosen H, Rosenberg R, Royall D, Sano M, Saykin A, Schellenberg G, Schneider J, Schneider L, Seeley W, Sherva R, Shibata D, Small S, Smith A, Smith J, Song Y, Spina S, St George‐Hyslop P, Stern R, Stevens A, Strittmatter S, Sultzer D, Swerdlow R, Teich A, Tilson J, Tosto G, Trojanowski J, Troncoso J, Tsuang D, Valladares O, Van Deerlin V, Van Dyck C, Van Eldik L, Vance J, Vardarajan B, Vassar R, Vinters H, Wang L, Weintraub S, Welsh‐Bohmer K, Wheeler N, Wijsman E, Wilhelmsen K, Williams B, Williamson J, Wilms H, Wingo T, Wisniewski T, Woltjer R, Woon M, Younkin S, Yu L, Zhao Y, Zhou X, Zhu C, Aizenstein H, Ances B, Andrews H, Bell K, Birn R, Brickman A, Bulova P, Cheema A, Chen K, Christian B, Clare I, Cohen A, Constantino J, Doran E, Fagan A, Feingold E, Foroud T, Handen B, Harp J, Hartley S, Head E, Henson R, Hom C, Honig L, Ikonomovic M, Johnson S, Jordan C, Kamboh M, Keator D, Klunk W, Kofler J, Krinsky‐McHale S, Lai F, Lao P, Laymon C, Lee J, Lott I, Lupson V, Mapstone M, Mathis C, Minhas D, Nadkarni N, O'Bryant S, Parisi M, Pang D, Petersen M, Price J, Pulsifer M, Rafii M, Reiman E, Rizvi B, Rosas H, Ryan L, Schmitt F, Schupf N, Silverman W, Tudorascu D, Tumuluru R, Varadarajan B, White D, Yassa M, Zaman S, Zhang F. Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 2670-2679. PMID: 38380866, PMCID: PMC11032545, DOI: 10.1002/alz.13718.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseGenes associated with late-onset Alzheimer's diseaseLate-onset Alzheimer's disease riskSeveral single nucleotide polymorphismsVariants associated with late-onset Alzheimer diseaseBeta-amyloidIdentified several single nucleotide polymorphismsWhole-genome sequence analysisGenome sequence analysisLevels of beta-amyloidAlzheimer's diseaseTight linkage disequilibriumMicrotubule associated proteinSingle nucleotide polymorphismsFamily studiesCandidate lociMTUS2Linkage disequilibriumSequence analysisAssociation analysisNucleotide polymorphismsGenetic associationAlzheimer's dementiaAssociated proteinGenetic componentReduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase
Takahashi H, Bhagwagar S, Nies S, Ye H, Han X, Chiasseu M, Wang G, Mackenzie I, Strittmatter S. Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase. Nature Communications 2024, 15: 1434. PMID: 38365772, PMCID: PMC10873339, DOI: 10.1038/s41467-024-45692-3.Peer-Reviewed Original ResearchConceptsTau inclusionsComorbid proteinopathiesTau aggregation in vitroPromotes tau aggregation in vitroAlzheimer's diseaseProgranulin reductionTDP-43 proteinopathyTauopathy phenotypeTau aggregationAD-tauHuman tauopathiesNeurofibrillary tanglesTauopathy miceReduction of progranulinPurified GlcCerTDP-43Concomitant accumulationAggregation in vitroAssociated with synucleinopathiesNeurodegenerative disordersProteinopathiesGCase inhibitionTauGCaseGlcCer
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 ageTMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury
Shafit-Zagardo B, Sidoli S, Goldman J, DuBois J, Corboy J, Strittmatter S, Guzik H, Edema U, Arackal A, Botbol Y, Merheb E, Nagra R, Graff S. TMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury. Cells 2023, 12: 1734. PMID: 37443768, PMCID: PMC10340176, DOI: 10.3390/cells12131734.Peer-Reviewed Original ResearchConceptsAxonal damageMultiple sclerosisRelapsing-remitting multiple sclerosisHypomorphic miceExperimental autoimmune encephalomyelitisRelapsing-remitting MSNormal-appearing white matterMultiple sclerosis plaquesWhite matter plaquesNon-neurologic controlsWild-type miceBrains of individualsLipid droplet accumulationAutoimmune encephalomyelitisMyelin oligodendrocyteCNS injuryLipid clearanceSpinal cordNeuronal integrityTransmembrane protein 106BWhite matterAlzheimer's diseaseMice resultsDroplet accumulationPlaquesLongitudinal simultaneous fMRI and mesoscale calcium imaging in a mouse model of Alzheimer’s disease
Mandino F, Shen X, Desrosiers-Gregoire G, O'Connor D, Mukherjee B, DeLuca K, Hamodi A, Owens A, Ha Y, Qu A, Onofrey J, Papademetris X, Chakravarty M, Crair M, Strittmatter S, Lake E. Longitudinal simultaneous fMRI and mesoscale calcium imaging in a mouse model of Alzheimer’s disease. Proceedings Of The International Society For Magnetic Resonance In Medicine ... Scientific Meeting And Exhibition. 2023 DOI: 10.58530/2023/3914.Peer-Reviewed Original ResearchMouse model of Alzheimer's diseaseModel of Alzheimer's diseaseMesoscale calcium imagingAlzheimer's diseaseBehavioral deficitsExcitatory neural activityMultimodal neuroimagingBOLD signalSimultaneous fMRINeuroimaging changesNeural activityBOLD fMRIPreliminary evidenceCalcium imagingClinically accessible biomarkersMesoscopic calcium imagingSpontaneous activityFMRINeuroimagingBOLDDeficitsComplex relationshipDecreased 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 kineticsPrion Protein Complex with mGluR5 Mediates Amyloid-ß Synaptic Loss in Alzheimer’s Disease
Roseman G, Fu L, Strittmatter S. Prion Protein Complex with mGluR5 Mediates Amyloid-ß Synaptic Loss in Alzheimer’s Disease. 2023, 467-481. DOI: 10.1007/978-3-031-20565-1_22.ChaptersAlzheimer's diseaseMouse modelAD transgenic mouse modelLong-term potentiation impairmentPrimary histopathological featureAD mouse modelAmyloid-beta plaquesTransgenic mouse modelPotential therapeutic targetSynaptic lossHistopathological featuresAD pathophysiologyNeuronal dysfunctionSynapse densityCognitive dysfunctionNeurofibrillary tanglesTherapeutic targetMemory deficitsCellular prion proteinMGluR5DiseaseCell death characteristicCommon formSynaptotoxicityDysfunction
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
2021
Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells
Franjic D, Skarica M, Ma S, Arellano JI, Tebbenkamp ATN, Choi J, Xu C, Li Q, Morozov YM, Andrijevic D, Vrselja Z, Spajic A, Santpere G, Li M, Zhang S, Liu Y, Spurrier J, Zhang L, Gudelj I, Rapan L, Takahashi H, Huttner A, Fan R, Strittmatter SM, Sousa AMM, Rakic P, Sestan N. Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron 2021, 110: 452-469.e14. PMID: 34798047, PMCID: PMC8813897, DOI: 10.1016/j.neuron.2021.10.036.Peer-Reviewed Original ResearchConceptsDisease-related proteinsCellular diversityCross-species analysisSingle-nucleus transcriptomesLipid droplet proteinsSpecies-specific propertiesImmature neuron populationTranscriptomic taxonomyAlzheimer's disease-related proteinsEndoplasmic reticulumCell typesHuman neuronsSpecies differencesHistologic signatureNeurogenic capabilityProteinExcitatory neuronsDiversityAdult miceGranule cellsAlzheimer's diseaseNeuron populationsCognitive functionEntorhinal cellsAdult humansSpreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-β
Nies SH, Takahashi H, Herber CS, Huttner A, Chase A, Strittmatter SM. Spreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-β. Journal Of Biological Chemistry 2021, 297: 101159. PMID: 34480901, PMCID: PMC8477193, DOI: 10.1016/j.jbc.2021.101159.Peer-Reviewed Original ResearchConceptsTau seedsAlzheimer's diseaseAD model miceWT mouse brainPathological tauSynaptic lossTau accumulationWT miceMouse tauTau pathologyTau burdenModel miceTau inclusionsPharmacological interventionsAD riskCognitive declineMouse brainTau aggregatesPyk2 kinaseKnowledge of factorsKinase inhibitorsMiceFyn kinase inhibitorAβMouse aging
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 efficacyGene-environment interaction promotes Alzheimer's risk as revealed by synergy of repeated mild traumatic brain injury and mouse App knock-in
Chiasseu M, Fesharaki-Zadeh A, Saito T, Saido TC, Strittmatter SM. Gene-environment interaction promotes Alzheimer's risk as revealed by synergy of repeated mild traumatic brain injury and mouse App knock-in. Neurobiology Of Disease 2020, 145: 105059. PMID: 32858147, PMCID: PMC7572902, DOI: 10.1016/j.nbd.2020.105059.Peer-Reviewed Original ResearchConceptsMild traumatic brain injuryTraumatic brain injuryAlzheimer's diseaseBrain injuryGene-environment interactionsMild closed head injuryMorris water maze testAge-matched wild-type controlsStrong unmet needAccumulation of amyloidAge-matched miceClosed head injuryWater maze testNovel object recognitionPersistent cognitive deficitsProtein gene mutationsIba1 expressionWild-type controlsPhospho-tauClinical manifestationsAD pathologyAD symptomsHead injuryAD pathogenesisRisk factorsPET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex
2019
Effect of AZD0530 on Cerebral Metabolic Decline in Alzheimer Disease
van Dyck CH, Nygaard HB, Chen K, Donohue MC, Raman R, Rissman RA, Brewer JB, Koeppe RA, Chow TW, Rafii MS, Gessert D, Choi J, Turner RS, Kaye JA, Gale SA, Reiman EM, Aisen PS, Strittmatter SM. Effect of AZD0530 on Cerebral Metabolic Decline in Alzheimer Disease. JAMA Neurology 2019, 76: 1219-1229. PMID: 31329216, PMCID: PMC6646979, DOI: 10.1001/jamaneurol.2019.2050.Peer-Reviewed Original ResearchAZD0530 treatmentAdverse eventsPrimary outcomeTreatment groupsAlzheimer's Disease Cooperative Study-ActivitiesAlzheimer's diseasePositron emission tomography evidenceMini-Mental State Examination scoreAlzheimer's Disease Assessment Scale-cognitive subscaleCerebral metabolic declineFrequent adverse eventsSecondary end pointsCerebral metabolic rateMild Alzheimer's dementiaState Examination scorePlasma drug levelsClinical Dementia RatingVolumetric magnetic resonanceEffect of AZD0530Neuronal cell surfaceModified intentionTreat populationSecondary outcomesNeuropsychiatric InventoryEfficacy analysisIn 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 subjectsSystematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance
Smith LM, Kostylev MA, Lee S, Strittmatter SM. Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance. Journal Of Biological Chemistry 2019, 294: 6042-6053. PMID: 30787106, PMCID: PMC6463724, DOI: 10.1074/jbc.ra118.006252.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAD brainLeukocyte immunoglobulin-like receptorsNogo receptor 1Human AD brainsImmunoglobulin-like receptorsB member 2Brains of individualsReceptor candidatesSoluble AβOsDisease relevanceCell surface expressionHippocampal neuronsMouse modelSynthetic AβAβO bindingMemory impairmentReceptor 1Cellular prion proteinNeuronal synapsesNgR1Molecular pathologyAβAβ speciesMember 2Rescue of Transgenic Alzheimer’s Pathophysiology by Polymeric Cellular Prion Protein Antagonists
Gunther EC, Smith LM, Kostylev MA, Cox TO, Kaufman AC, Lee S, Folta-Stogniew E, Maynard GD, Um JW, Stagi M, Heiss JK, Stoner A, Noble GP, Takahashi H, Haas LT, Schneekloth JS, Merkel J, Teran C, Naderi Z, Supattapone S, Strittmatter SM. Rescue of Transgenic Alzheimer’s Pathophysiology by Polymeric Cellular Prion Protein Antagonists. Cell Reports 2019, 26: 145-158.e8. PMID: 30605671, PMCID: PMC6358723, DOI: 10.1016/j.celrep.2018.12.021.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseOligomeric β-amyloid peptideAPPswe/PS1ΔE9 transgenic miceEffective brain concentrationsPotential therapeutic approachΒ-amyloid peptideBrain concentrationsSynapse lossTherapeutic approachesAlzheimer's pathophysiologyTransgenic miceScN2a cellsMemory deficitsCellular prion proteinPathophysiologyTransmissible spongiformAβOsProtein antagonistLow nanomolar affinityDiseasePrPPrion proteinNanomolar affinitySupAntagonist