2025
Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease
Cai Y, Kanyo J, Wilson R, Bathla S, Cardozo P, Tong L, Qin S, Fuentes L, Pinheiro-de-Sousa I, Huynh T, Sun L, Mansuri M, Tian Z, Gan H, Braker A, Trinh H, Huttner A, Lam T, Petsalaki E, Brennand K, Nairn A, Grutzendler J. Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease. Nature Aging 2025, 5: 504-527. PMID: 40065072, PMCID: PMC11922768, DOI: 10.1038/s43587-025-00823-3.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProximity labeling approachIPSC-derived neuronsSubcellular proteomicsCytoskeleton dynamicsPhosphorylated mTOR levelsDystrophic neuritesLipid transportBiological processesProtein turnoverAD modelHuman induced pluripotent stem cellsAmyloid depositsIPSC modelsProteomicsInduced pluripotent stem cellsPluripotent stem cellsMTOR inhibitionTherapeutic targetAxonal pathologyLabeling approachMTOR levelsMouse brainSpheroid formationAlzheimer
2024
Neuroinflammation in Alzheimer disease
Heneka M, van der Flier W, Jessen F, Hoozemanns J, Thal D, Boche D, Brosseron F, Teunissen C, Zetterberg H, Jacobs A, Edison P, Ramirez A, Cruchaga C, Lambert J, Laza A, Sanchez-Mut J, Fischer A, Castro-Gomez S, Stein T, Kleineidam L, Wagner M, Neher J, Cunningham C, Singhrao S, Prinz M, Glass C, Schlachetzki J, Butovsky O, Kleemann K, De Jaeger P, Scheiblich H, Brown G, Landreth G, Moutinho M, Grutzendler J, Gomez-Nicola D, McManus R, Andreasson K, Ising C, Karabag D, Baker D, Liddelow S, Verkhratsky A, Tansey M, Monsonego A, Aigner L, Dorothée G, Nave K, Simons M, Constantin G, Rosenzweig N, Pascual A, Petzold G, Kipnis J, Venegas C, Colonna M, Walter J, Tenner A, O’Banion M, Steinert J, Feinstein D, Sastre M, Bhaskar K, Hong S, Schafer D, Golde T, Ransohoff R, Morgan D, Breitner J, Mancuso R, Riechers S. Neuroinflammation in Alzheimer disease. Nature Reviews Immunology 2024, 1-32. PMID: 39653749, DOI: 10.1038/s41577-024-01104-7.Peer-Reviewed Original ResearchAlzheimer's diseasePathogenesis of Alzheimer's diseaseMultiple lines of informationGenetic studiesInfluence of geneticsLines of informationCell typesDisease developmentDementia-causing diseasesStages of Alzheimer's diseasePathological roleMultiple linesTherapeutic strategiesImmune processesPreclinical stage of Alzheimer's diseaseCellsAdaptive immune activationTargeting neuroinflammationPathological mechanismsLifestyle factorsGeneticsmTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis
Min W, Qin L, Zhang H, López-Giráldez F, Jiang N, Kim Y, Mohan V, Su M, Murray K, Grutzendler J, Zhou J. mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis. Circulation Research 2024, 135: e94-e113. PMID: 38957991, PMCID: PMC11293987, DOI: 10.1161/circresaha.123.324015.Peer-Reviewed Original ResearchCerebral vascular malformationsEndothelial progenitor cellsBlood-brain barrier integritySingle-cell RNA sequencing analysisDisruption of blood-brain barrier integrityBarrier integrityResident endothelial progenitor cellsRNA sequencing analysisTissue immunofluorescence analysisEndothelial cellsEPC clustersStem cell markersFocal neurological deficitsBrain's neurovascular unitMTOR signalingHuman CCM lesionsMTORC1 signalingBlood-brain barrierCapillary endothelial cellsCCM pathogenesisVascular malformationsLesion signaturesNeurological deficitsCell markersClonal expansion
2023
Single cell in vivo optogenetic stimulation by two-photon excitation fluorescence transfer
Tong L, Han S, Xue Y, Chen M, Chen F, Ke W, Shu Y, Ding N, Bewersdorf J, Zhou Z, Yuan P, Grutzendler J. Single cell in vivo optogenetic stimulation by two-photon excitation fluorescence transfer. IScience 2023, 26: 107857. PMID: 37752954, PMCID: PMC10518705, DOI: 10.1016/j.isci.2023.107857.Peer-Reviewed Original Research
2022
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 mannerDysfunctionOligodendroglial macroautophagy is essential for myelin sheath turnover to prevent neurodegeneration and death
Aber ER, Griffey CJ, Davies T, Li AM, Yang YJ, Croce KR, Goldman JE, Grutzendler J, Canman JC, Yamamoto A. Oligodendroglial macroautophagy is essential for myelin sheath turnover to prevent neurodegeneration and death. Cell Reports 2022, 41: 111480. PMID: 36261002, PMCID: PMC9639605, DOI: 10.1016/j.celrep.2022.111480.Peer-Reviewed Original ResearchConceptsCell typesLive-cell imagingNeurodegenerative disease pathophysiologySuch cell typesMouse geneticsAdult-onset neurodegenerative diseaseMacroautophagyCell imagingNeurodegenerative diseasesMyelin proteinsNeurodegenerationDisease pathophysiologyTurnoverMature oligodendrocytesCentral nervous systemAmphisomesMyelin sheath structureNeural functionNervous systemMyelin turnoverGeneticsMyelin sheathProgressive motor declineProteinHomeostasisKCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling
Ando K, Tong L, Peng D, Vázquez-Liébanas E, Chiyoda H, He L, Liu J, Kawakami K, Mochizuki N, Fukuhara S, Grutzendler J, Betsholtz C. KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling. Developmental Cell 2022, 57: 1383-1399.e7. PMID: 35588738, DOI: 10.1016/j.devcel.2022.04.019.Peer-Reviewed Original ResearchConceptsK-ATP channel functionVascular smooth muscle cell differentiationChannel functionSmooth muscle cell differentiationMuscle cell differentiationVascular smooth muscle developmentSmooth muscle developmentVSMC developmentHuman central nervous system disordersMuscle developmentVSMC differentiationCentral nervous system disordersCell differentiationChemical inhibitionVoltage-dependent calcium channelsATP-sensitive potassium channelsFunction mutationsCell progenitorsK-ATP channelsCerebral blood flowCell culture modelMolecular causesNervous system disordersIntracellular CaVasoconstrictive capacity
2021
Intravital Imaging of Neocortical Heterotopia Reveals Aberrant Axonal Pathfinding and Myelination around Ectopic Neurons
Li AM, Hill RA, Grutzendler J. Intravital Imaging of Neocortical Heterotopia Reveals Aberrant Axonal Pathfinding and Myelination around Ectopic Neurons. Cerebral Cortex 2021, 31: 4340-4356. PMID: 33877363, PMCID: PMC8328209, DOI: 10.1093/cercor/bhab090.Peer-Reviewed Original ResearchConceptsNeuronal clustersEarly postnatal developmentVivo calcium imagingEctopic neuronal clustersAxonal patternNeocortical heterotopiaHeterotopic neuronsCortical heterotopiaHeterotopia formationEctopic neuronsAnimal modelsTractable animal modelPostnatal developmentCalcium imagingBrain regionsInducible modelIntravital imagingNeuronsAxonal pathfindingAberrant patternsHeterotopiaMyelinationAxon guidanceCognitive disabilitiesLive mice3D super-resolution deep-tissue imaging in living mice
Velasco MGM, Zhang M, Antonello J, Yuan P, Allgeyer ES, May D, M’Saad O, Kidd P, Barentine AES, Greco V, Grutzendler J, Booth MJ, Bewersdorf J. 3D super-resolution deep-tissue imaging in living mice. Optica 2021, 8: 442-450. PMID: 34239948, PMCID: PMC8243577, DOI: 10.1364/optica.416841.Peer-Reviewed Original ResearchWater-immersion objective lensTwo-photon excitationSuper-resolution imagingEmission depletion (STED) microscopyAdaptive opticsSTED systemObjective lensOptical aberrationsDepletion microscopyBiological tissuesNanoscale structuresLiving mouseOrganic dyesOpticsSTEDExcitationMouse brain tissueLiving cellsThree-dimensional visualizationMicroscopyLightUnique insightsImagingLensUnlocking Pericyte Function in the Adult Blood Brain Barrier One Cell at a Time
Nicoli S, Grutzendler J. Unlocking Pericyte Function in the Adult Blood Brain Barrier One Cell at a Time. Circulation Research 2021, 128: 511-512. PMID: 33600230, PMCID: PMC7928238, DOI: 10.1161/circresaha.121.318799.Peer-Reviewed Original ResearchCaveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model
Zhou HJ, Qin L, Jiang Q, Murray KN, Zhang H, Li B, Lin Q, Graham M, Liu X, Grutzendler J, Min W. Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model. Nature Communications 2021, 12: 504. PMID: 33495460, PMCID: PMC7835246, DOI: 10.1038/s41467-020-20774-0.Peer-Reviewed Original ResearchConceptsCerebral cavernous malformationsCCM lesionsSmooth muscle actin-positive pericytesEndothelial cell lossRegions of brainCCM pathogenesisPost-capillary venulesCerebral hemorrhagePharmacological blockadeVascular abnormalitiesEC-specific deletionCavernous malformationsMouse modelCell lossMicrovascular bedGenetic deletionLesion formationLesionsVascular dynamicsBarrier functionMicrovascular structureTwo-photon microscopyTie2PathogenesisMice
2020
Imaging and optogenetic modulation of vascular mural cells in the live brain
Tong L, Hill RA, Damisah EC, Murray KN, Yuan P, Bordey A, Grutzendler J. Imaging and optogenetic modulation of vascular mural cells in the live brain. Nature Protocols 2020, 16: 472-496. PMID: 33299155, DOI: 10.1038/s41596-020-00425-w.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRegional cerebral blood flowMural cellsBlood-brain barrier maintenanceCerebral ischemia mouse modelAge-related neurodegenerative diseasesCerebral blood flowSmooth muscle cell physiologyBrain blood vesselsIschemia mouse modelVascular mural cellsBrain microvesselsHigh-resolution intravital imagingVascular disordersMouse modelBlood flowMuscle cell physiologyTransgenic miceCalcium transientsAlzheimer's diseaseCalcium imagingCell subtypesBarrier maintenanceNeurodegenerative diseasesTwo-photon optogeneticsBlood vesselsAstrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
Damisah EC, Hill RA, Rai A, Chen F, Rothlin CV, Ghosh S, Grutzendler J. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Science Advances 2020, 6: eaba3239. PMID: 32637606, PMCID: PMC7319765, DOI: 10.1126/sciadv.aba3239.Peer-Reviewed Original ResearchConceptsCorpse removalPrecise spatiotemporal resolutionApoptotic cell removalReceptor tyrosine kinasesGlial cellsOrchestrated rolesTyrosine kinaseApoptotic bodiesCell deathSpecialized roleCoordinated interactionPhagocytic interactionSingle cellsBrain homeostasisCellsCell removalIntravital optical imagingSpatiotemporal resolutionRole of phagocytesSynchronized fashionKinaseMarked delayRoleHomeostasisAstrocytesTREM2: Modulator of Lipid Metabolism in Microglia
Damisah EC, Rai A, Grutzendler J. TREM2: Modulator of Lipid Metabolism in Microglia. Neuron 2020, 105: 759-761. PMID: 32135085, DOI: 10.1016/j.neuron.2020.02.008.Peer-Reviewed Original ResearchEmerging technologies to study glial cells
Hirbec H, DĂ©glon N, Foo LC, Goshen I, Grutzendler J, Hangen E, Kreisel T, Linck N, Muffat J, Regio S, Rion S, Escartin C. Emerging technologies to study glial cells. Glia 2020, 68: 1692-1728. PMID: 31958188, DOI: 10.1002/glia.23780.Peer-Reviewed Original ResearchConceptsCell typesChallenging biological questionsGlial cellsSpecific cell typesDifferent glial cell typesGlial cell typesBiological questionsPhysiological functionsPrecursor cellsTight interactionOligodendrocyte precursor cellsCellsExperimental approachRelative contributionBrain functionFull understandingSpecific brain functionsRoleFunctionInteractionDevelopmentTranslation
2019
Cellular Control of Brain Capillary Blood Flow: In Vivo Imaging Veritas
Grutzendler J, Nedergaard M. Cellular Control of Brain Capillary Blood Flow: In Vivo Imaging Veritas. Trends In Neurosciences 2019, 42: 528-536. PMID: 31255380, PMCID: PMC7386067, DOI: 10.1016/j.tins.2019.05.009.Peer-Reviewed Original ResearchConceptsCapillary blood flowBlood flowBrain capillary blood flowRegional cerebral blood flowCerebral blood flowRed blood cell deformabilityBlood cell deformabilityMicrovascular perfusionNeurovascular couplingMicrovascular flowBrain metabolitesMural cellsLevel-dependent changesNeural activationVessel diameterMicrovascular treeNeural activityCell deformabilityCell controlDirect visualizationMethodological standardsVasomotilityPerfusionControlUncovering the biology of myelin with optical imaging of the live brain
Hill RA, Grutzendler J. Uncovering the biology of myelin with optical imaging of the live brain. Glia 2019, 67: 2008-2019. PMID: 31033062, PMCID: PMC6744352, DOI: 10.1002/glia.23635.Peer-Reviewed Original Research
2018
Publisher Correction: Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes
Shahbazi A, Kinnison J, Vescovi R, Du M, Hill R, Joesch M, Takeno M, Zeng H, da Costa NM, Grutzendler J, Kasthuri N, Scheirer WJ. Publisher Correction: Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes. Scientific Reports 2018, 8: 17585. PMID: 30498261, PMCID: PMC6265300, DOI: 10.1038/s41598-018-36220-7.Peer-Reviewed Original ResearchFlexible Learning-Free Segmentation and Reconstruction of Neural Volumes
Shahbazi A, Kinnison J, Vescovi R, Du M, Hill R, Joesch M, Takeno M, Zeng H, da Costa NM, Grutzendler J, Kasthuri N, Scheirer WJ. Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes. Scientific Reports 2018, 8: 14247. PMID: 30250218, PMCID: PMC6155135, DOI: 10.1038/s41598-018-32628-3.Peer-Reviewed Original ResearchConceptsGigabytes of dataSupervised learning methodsHigh-energy synchrotron X-ray microtomographyHigh-quality reconstructionComputer visionHigh biological fidelityVirtual eyeSpectral confocal reflectance microscopyStack of imagesLearning methodsPipeline reconstructionContextual cluesDifferent modalitiesNeural volumeMouse datasetsBiological fidelityImagesData collectionPipelineGigabytesSegmentationMachineAlgorithmDatasetSufficient qualityLifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain
Hill RA, Li AM, Grutzendler J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nature Neuroscience 2018, 21: 683-695. PMID: 29556031, PMCID: PMC5920745, DOI: 10.1038/s41593-018-0120-6.Peer-Reviewed Original ResearchConceptsMyelin degenerationYears of ageAge-related degenerationMyelin plasticityMyelin remodelingNeural processing speedBrain pathogenesisOligodendrocyte deathUnmyelinated axonsAxonal myelinMyelin coverageStructural remodelingMouse cortexMammalian brainPeak myelinationOligodendrocyte generationIndividual axonsMyelinating oligodendrocytesMyelin distributionDegenerationMyelin internodesNetwork homeostasisAxonsStructural plasticityRemodeling
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply