2016
O2‐07‐02: Trem2‐Mediated Early Response by Resident Microglia Limits Diffusion and Toxicity of Amyloid Plaques
Wang Y, Ulland T, Ulrich J, Song W, Yuan P, Mahan T, Shi Y, Gilfillan S, Cella M, DeMattos R, Grutzendler J, Cirrito J, Holtzman D, Colonna M. O2‐07‐02: Trem2‐Mediated Early Response by Resident Microglia Limits Diffusion and Toxicity of Amyloid Plaques. Alzheimer's & Dementia 2016, 12: p241-p242. DOI: 10.1016/j.jalz.2016.06.431.Peer-Reviewed Original ResearchAmyloid plaquesEarly responseTREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
Wang Y, Ulland TK, Ulrich JD, Song W, Tzaferis JA, Hole JT, Yuan P, Mahan TE, Shi Y, Gilfillan S, Cella M, Grutzendler J, DeMattos RB, Cirrito JR, Holtzman DM, Colonna M. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. Journal Of Experimental Medicine 2016, 213: 667-675. PMID: 27091843, PMCID: PMC4854736, DOI: 10.1084/jem.20151948.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseTREM2 deficiencyAβ accumulationNeuritic damageAβ plaquesMyeloid cellsAbsence of TREM2Impact of TREM2Rare TREM2 variantsAmyloid β accumulationBrain-resident microgliaMyeloid cells 2Peripheral blood monocytesEarly time pointsMicroglial clusteringMicroglial receptorΒ accumulationAβ depositsNeuronal degenerationTREM2 variantsAmyloid plaquesMurine modelBlood monocytesMatter of debateMicrogliaAttenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity
Yuan P, Grutzendler J. Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity. Journal Of Neuroscience 2016, 36: 632-641. PMID: 26758850, PMCID: PMC4710779, DOI: 10.1523/jneurosci.2531-15.2016.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCalcium-Binding ProteinsClozapineDesigner DrugsDisease Models, AnimalHumansInsulysinLysosome-Associated Membrane GlycoproteinsMaleMiceMice, TransgenicMicrofilament ProteinsNerve Tissue ProteinsNeurotoxicity SyndromesPresenilin-1Proto-Oncogene Proteins c-fosStyrenesTransduction, GeneticConceptsAmyloid plaquesAlzheimer's diseaseNeuronal activityAmyloid depositionDisease miceNeural activityAD-like mouse modelNeural activity reductionΒ-amyloid depositionAlzheimer's disease miceNovel therapeutic approachesPotential therapeutic strategyViral-mediated deliveryChemogenetic modulationSynaptic lossAβ depositionSynaptic pathologyNeural hyperactivityAmyloid pathologyAxonal dystrophyDendritic fieldsChronic attenuationDesigner receptorsTherapeutic approachesMouse model
2015
Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer’s disease amyloid plaques
Gowrishankar S, Yuan P, Wu Y, Schrag M, Paradise S, Grutzendler J, De Camilli P, Ferguson SM. Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer’s disease amyloid plaques. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e3699-e3708. PMID: 26124111, PMCID: PMC4507205, DOI: 10.1073/pnas.1510329112.Peer-Reviewed Original ResearchConceptsAmyloid plaquesNeuronal lysosomesAlzheimer's diseaseAlzheimer's disease brain pathologyLysosome accumulationAlzheimer's disease (AD) amyloid plaquesΒ-amyloid depositionΒ-amyloid depositsAmyloid precursor proteinLysosome-like organellesRetrograde axonal transportWild-type brainsSuch axonsSwollen axonsMassive accumulationAxonal lysosomesBrain pathologyAmyloidogenic processingMouse modelAmyloid depositsLuminal proteasesAxonal transportLocal impairmentNeuronal processesNeurodegenerative diseases
2011
Multicolor time-stamp reveals the dynamics and toxicity of amyloid deposition
Condello C, Schain A, Grutzendler J. Multicolor time-stamp reveals the dynamics and toxicity of amyloid deposition. Scientific Reports 2011, 1: 19. PMID: 22355538, PMCID: PMC3216507, DOI: 10.1038/srep00019.Peer-Reviewed Original ResearchConceptsPlaque burdenAmyloid depositionAlzheimer's diseaseAD mouse modelPlaque enlargementClinicopathological studyNeuritic dystrophyPathogenic rolePostmortem studiesAmyloid plaquesNew plaquesConsequent neurotoxicityMouse modelOld plaquesQuantitative confocal imagingCognitive statusPlaquesPlaque expansionOld animalsAmyloid-binding dyesNeurotoxicityDiseasePoor correlationBurdenCritical determinant
2007
Various Dendritic Abnormalities Are Associated with Fibrillar Amyloid Deposits in Alzheimer's Disease
GRUTZENDLER J, HELMIN K, TSAI J, GAN W. Various Dendritic Abnormalities Are Associated with Fibrillar Amyloid Deposits in Alzheimer's Disease. Annals Of The New York Academy Of Sciences 2007, 1097: 30-39. PMID: 17413007, DOI: 10.1196/annals.1379.003.Peer-Reviewed Original ResearchConceptsAmyloid depositsAlzheimer's diseasePSAPP miceFibrillar amyloid depositsAmyloid depositionDendritic abnormalitiesHuman AD tissueFibrillar amyloid depositionHuman AD brainsTransgenic mouse modelHuman postmortem brainDystrophic neuritesSpine lossAD brainAD tissueAmyloid plaquesCommon abnormalityMouse modelPostmortem brainsDendritic spinesNeuronal circuitsVaricosity formationSynaptic structureDiseaseDendritic branches
2004
Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches
Tsai J, Grutzendler J, Duff K, Gan WB. Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Nature Neuroscience 2004, 7: 1181-1183. PMID: 15475950, DOI: 10.1038/nn1335.Peer-Reviewed Original ResearchConceptsFibrillar amyloid depositionAmyloid depositionAlzheimer's diseaseTransgenic mouse modelImportance of preventionFibrillar amyloid depositsSpine lossNearby axonsNeuronal labelingEarly clearanceLarge varicositiesAmyloid plaquesMouse modelNeuronal circuitryAmyloid depositsTwo-photon imagingNeuronal connectionsSynaptic abnormalitiesNeuronal branchesPermanent disruptionPlaquesDiseaseAtrophyVaricositiesPathogenesis