Featured Publications
PLD3 affects axonal spheroids and network defects in Alzheimer’s disease
Yuan P, Zhang M, Tong L, Morse T, McDougal R, Ding H, Chan D, Cai Y, Grutzendler J. PLD3 affects axonal spheroids and network defects in Alzheimer’s disease. Nature 2022, 612: 328-337. PMID: 36450991, PMCID: PMC9729106, DOI: 10.1038/s41586-022-05491-6.Peer-Reviewed Original ResearchConceptsAxonal spheroidsAlzheimer's diseaseConduction blockadeNeural circuit abnormalitiesNeural network dysfunctionAmyloid removalCircuit abnormalitiesAge-dependent accumulationNetwork dysfunctionEndolysosomal vesiclesMouse modelNeuronal overexpressionCognitive declineAxonal connectivityDiseasePrecise mechanismBlockadePLD3Neural network functionSpheroid growthSevere disruptionCurrent sinkVoltage imagingSize-dependent mannerDysfunctionMicroglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello C, Yuan P, Grutzendler J. Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging. Biological Psychiatry 2017, 83: 377-387. PMID: 29169609, PMCID: PMC5767550, DOI: 10.1016/j.biopsych.2017.10.007.Peer-Reviewed Original ResearchConceptsAlzheimer's diseasePlaque compactionAmyloid depositsInvolvement of microgliaPlaque-associated microgliaLate-onset Alzheimer's diseaseMyeloid cells 2Onset Alzheimer's diseaseMicroglia receptorMicroglia polarizationAD neuropathologyAxonal pathologyNeuroprotective functionDisease progressionOptical imaging studiesCurrent evidenceAD riskMicrogliaTherapeutic targetingAdjacent axonsImaging studiesCells 2DiseasePrecise mechanismRecent genetic studiesTREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy
Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM, Luo W, Colonna M, Baddeley D, Grutzendler J. TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. Neuron 2016, 90: 724-739. PMID: 27196974, PMCID: PMC4898967, DOI: 10.1016/j.neuron.2016.05.003.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAxonal dystrophyAmyloid depositsAD-like miceHuman AD tissueLate-onset Alzheimer's diseaseNovel therapeutic strategiesTREM2 deficiencyTau hyperphosphorylationAD tissueMicroglia processesPharmacological modulationCompact plaquesTherapeutic strategiesHigh-resolution confocalTREM2 mutationsTREM2Barrier functionMiceGreater surface exposureAmyloid fibrilsHaplodeficiencyPlaquesDiseaseDystrophyMicroglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello C, Yuan P, Schain A, Grutzendler J. Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques. Nature Communications 2015, 6: 6176. PMID: 25630253, PMCID: PMC4311408, DOI: 10.1038/ncomms7176.Peer-Reviewed Original ResearchLabel-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy
Schain AJ, Hill RA, Grutzendler J. Label-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy. Nature Medicine 2014, 20: 443-449. PMID: 24681598, PMCID: PMC3981936, DOI: 10.1038/nm.3495.Peer-Reviewed Original Research
2017
Oxalate-curcumin–based probe for micro- and macroimaging of reactive oxygen species in Alzheimer’s disease
Yang J, Zhang X, Yuan P, Yang J, Xu Y, Grutzendler J, Shao Y, Moore A, Ran C. Oxalate-curcumin–based probe for micro- and macroimaging of reactive oxygen species in Alzheimer’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 12384-12389. PMID: 29109280, PMCID: PMC5703278, DOI: 10.1073/pnas.1706248114.Peer-Reviewed Original ResearchConceptsCerebral amyloid angiopathyAD brainAlzheimer's diseaseTwo-photon imagingNIRF imagingAmyloid-beta plaquesROS levelsIrreversible neurodegenerative disorderAD pathological conditionsAge-related increaseReactive oxygen species levelsAmyloid angiopathyBeta plaquesOxygen species levelsDrug treatmentHealthy brainNeurodegenerative disordersDiseaseOxidative stressHigh ROS levelsPathological conditionsReactive oxygen speciesBrainFluorescence imaging probeOxygen species
2016
Neurovascular and Immuno-Imaging: From Mechanisms to Therapies. Proceedings of the Inaugural Symposium
Akassoglou K, Agalliu D, Chang CJ, Davalos D, Grutzendler J, Hillman EM, Khakh BS, Kleinfeld D, McGavern DB, Nelson SJ, Zlokovic BV. Neurovascular and Immuno-Imaging: From Mechanisms to Therapies. Proceedings of the Inaugural Symposium. Frontiers In Neuroscience 2016, 10: 46. PMID: 26941593, PMCID: PMC4761864, DOI: 10.3389/fnins.2016.00046.Peer-Reviewed Original ResearchNeurovascular interfaceNeurological diseasesTherapeutic interventionsNovel targetInteractive symposiumPathological conditionsIntravital imagingVascular biologyNeurovascularVascular systemDiseaseBiological mechanismsRecent studiesUniversity of CaliforniaFundamental biological mechanismsSan FranciscoTherapyBrainInaugural symposiumImmunology
2014
A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease
Zhang X, Tian Y, Yuan P, Li Y, Yaseen MA, Grutzendler J, Moore A, Ran C. A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease. Chemical Communications 2014, 50: 11550-11553. PMID: 25134928, PMCID: PMC4617557, DOI: 10.1039/c4cc03731f.Peer-Reviewed Original Research
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
2006
Two-photon imaging of synaptic plasticity and pathology in the living mouse brain
Grutzendler J, Gan WB. Two-photon imaging of synaptic plasticity and pathology in the living mouse brain. Neurotherapeutics 2006, 3: 489-496. PMID: 17012063, PMCID: PMC3593400, DOI: 10.1016/j.nurx.2006.07.005.Peer-Reviewed Original ResearchConceptsTwo-photon microscopyMouse brainAcute brain injuryPostsynaptic dendritic spinesAdult mouse brainCerebral ischemiaSynaptic pathologyCerebrovascular diseaseBrain injuryMouse modelDendritic spinesAnimal modelsBrain cellsIntact brainTwo-photon imagingNeuronal connectionsSynaptic plasticityAlzheimer's diseaseNeuronal structuresDiseaseBrainStructural plasticityPathologyTechnical considerationsIschemia
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
2001
Cholinesterase Inhibitors for Alzheimer’s Disease
Grutzendler J, Morris J. Cholinesterase Inhibitors for Alzheimer’s Disease. Drugs 2001, 61: 41-52. PMID: 11217870, DOI: 10.2165/00003495-200161010-00005.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseCholinesterase inhibitorsCommon age-related neurodegenerative diseaseDifferent safety profilesAvailability of acetylcholineUrgent public health problemAge-related neurodegenerative diseasesModerate Alzheimer's diseasePublic health problemPossible adverse effectsPrimary therapySymptomatic treatmentSafety profileChEIsCentral synapsesClinical experienceUS FoodDrug AdministrationHealth problemsBasic neurobiologyCognitive statusNeurodegenerative diseasesPatientsDiseaseAdverse effects