2024
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerability
2023
Mass spectrometry on cerebrospinal fluid uncovers association of novel glycolysis biomarkers with Alzheimer’s disease in a complex clinical cohort
de Geus M, Leslie S, Wang W, Lam T, Broekman M, Neefjes S, Nairn A, Carlyle B, Arnold S. Mass spectrometry on cerebrospinal fluid uncovers association of novel glycolysis biomarkers with Alzheimer’s disease in a complex clinical cohort. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.078466.Peer-Reviewed Original ResearchAlzheimer's diseaseMild cognitive impairmentHospital neurology serviceNon-AD diagnosesDiagnostic lumbar puncturePrognosis of ADCerebrospinal fluid biomarkersClinic cohortFurther mechanistic studiesNeurology serviceFDG-PETBrain metabolismFluid biomarkersLumbar puncturePatient cohortClinical indicationsDisease progressionATN biomarkersClinical cohortTreatment responseComplex cohortBackground DiagnosisCSF samplesTreatment efficacyLinear regression analysis
2022
Applying Data‐Independent Acquisition Mass Spectrometry on Cerebrospinal Fluid Samples from a Neurology Clinic for Biomarker Discovery in Alzheimer’s Disease
de Geus M, Leslie S, Ramirez C, Trombetta B, Wang W, Lam T, Gotti C, Roux‐Dalvai F, Droit A, Nairn A, Arnold S, Carlyle B. Applying Data‐Independent Acquisition Mass Spectrometry on Cerebrospinal Fluid Samples from a Neurology Clinic for Biomarker Discovery in Alzheimer’s Disease. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.064314.Peer-Reviewed Original ResearchAlzheimer's diseaseMild cognitive impairmentPatient cohortAD-specific biomarkersNon-AD diagnosesPrognosis of ADCerebrospinal fluid samplesNeurology clinicBrain metabolismFluid biomarkersAD progressionCognitive prognosisComplex cohortBackground DiagnosisTreatment efficacyDementia diagnosisLarge-scale patient cohortsPathophysiological processesSpecific biomarkersRegulation of balanceDiagnosisCognitive AssessmentDiseaseCohortBiomarkers
2021
Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
Leslie SN, Kanyo J, Datta D, Wilson RS, Zeiss C, Duque A, Lam TT, Arnsten AFT, Nairn AC. Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates. Frontiers In Aging Neuroscience 2021, 13: 767322. PMID: 34867294, PMCID: PMC8637411, DOI: 10.3389/fnagi.2021.767322.Peer-Reviewed Original ResearchTau phosphorylationPrefrontal cortexAlzheimer's diseaseAge-related changesLayer III pyramidal cellsRhesus monkey prefrontal cortexSignificant risk factorsMonkey prefrontal cortexNon-human primatesAD pathologyTau levelsRisk factorsPyramidal cellsRodent modelsIdentifies ageRhesus monkeysLiquid chromatography-tandem mass spectrometryTherapeutic developmentNatural aging processSignificant increaseTauAgeDiseaseRobust labelingMonkeys
2014
Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, Ghosh D, Kanyo J, Zhang Y, Seyb K, Ononenyi C, Foscue E, Anderson GM, Gresack J, Cuny GD, Glicksman MA, Greengard P, Lam TT, Tautz L, Nairn AC, Ellman JA, Lombroso PJ. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease. PLOS Biology 2014, 12: e1001923. PMID: 25093460, PMCID: PMC4122355, DOI: 10.1371/journal.pbio.1001923.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmino Acid SequenceAnimalsBenzothiepinsCatalytic DomainCell DeathCerebral CortexCognition DisordersCysteineDisease Models, AnimalEnzyme InhibitorsHigh-Throughput Screening AssaysHumansMaleMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNeuronsPhosphorylationPhosphotyrosineProtein Tyrosine Phosphatases, Non-ReceptorSubstrate SpecificityConceptsInhibitors of stepsSpecificity of inhibitorsIsoxazolepropionic acid receptor (AMPAR) traffickingCatalytic cysteinePTP inhibitorsTyrosine phosphataseTyrosine phosphorylationSecondary assaysSTEP KO miceReceptor traffickingFirst large-scale effortN-methyl-D-aspartate receptorsPyk2 activitySTEP inhibitorLarge-scale effortsNovel therapeutic targetSynaptic functionAlzheimer's diseaseNeurodegenerative disordersCortical cellsTherapeutic targetERK1/2Specificity experimentsPhosphataseInhibitors