2023
Anatomical characterization of pT217‐tau in aged rhesus macaque association cortices: Relevance for trans‐synaptic propagation in sporadic Alzheimer’s Disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Anatomical characterization of pT217‐tau in aged rhesus macaque association cortices: Relevance for trans‐synaptic propagation in sporadic Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.075998.Peer-Reviewed Original ResearchTau pathologyEntorhinal cortexAlzheimer's diseaseRhesus macaquesBrain tau pathologyHigher brain circuitsHigher cortical circuitsPattern of neurodegenerationAged rhesus macaquesHuman Alzheimer's diseaseSporadic Alzheimer's diseaseTrans-synaptic propagationSoluble tau speciesSequence of tauDorsolateral prefrontal cortexAmyloid pathologyExtracellular spaceDendritic shaftsAdvanced neurodegenerationTau hyperphosphorylationInhibitory synapsesNeurofibrillary tanglesGlutamatergic synapsesSpine apparatusAD biomarkersChronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques
Bathla S, Datta D, Liang F, Barthelemy N, Wiseman R, Slusher B, Asher J, Zeiss C, Ekanayake‐Alper D, Holden D, Terwilliger G, Duque A, Arellano J, van Dyck C, Bateman R, Xie Z, Nairn A, Arnsten A. Chronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12431. PMID: 37915375, PMCID: PMC10617575, DOI: 10.1002/trc2.12431.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseEntorhinal cortexGCPII inhibitionDorsolateral prefrontal cortexChronic inhibitionTau pathologyTau hyperphosphorylationAged macaquesType 3 metabotropic glutamate receptorAlzheimer's diseasePrefrontal cortexRhesus macaquesVehicle-treated monkeysAged rhesus macaquesMetabotropic glutamate receptorsApparent side effectsAmyloid beta 1Regulation of calciumGCPII inhibitorsKey etiological factorGCPII activityPrimate dlPFCNeuronal damageCSF analysisCalcium dysregulation
2021
Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates
Datta D, Leslie SN, Wang M, Morozov YM, Yang S, Mentone S, Zeiss C, Duque A, Rakic P, Horvath TL, van Dyck C, Nairn AC, Arnsten AFT. Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates. Alzheimer's & Dementia 2021, 17: 920-932. PMID: 33829643, PMCID: PMC8195842, DOI: 10.1002/alz.12325.Peer-Reviewed Original ResearchConceptsTau pathologyCalcium leakTau phosphorylationNeuronal firingAlzheimer's diseaseEarly tau phosphorylationPyramidal cell dendritesSporadic Alzheimer's diseasePrimary cortical neuronsPotential therapeutic targetCognitive performanceAge-related reductionMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexNon-human primatesCalcium dysregulationCell dendritesCortical neuronsCalcium-binding proteinsAD biomarkersPathology markersTherapeutic targetAnimal modelsAged monkeysPrefrontal cortex
2020
Solanezumab in‐depth outcomes
Farlow M, Bateman R, Aschenbrenner A, Benzinger T, Clifford D, Coalier K, Cruchaga C, Fagan A, Goate A, Gordon B, Hassenstab J, Jack C, Koeppe R, McDade E, Mills S, Morris J, Salloway S, Santacruz A, Snyder P, Wang G, Xiong C, Snider B, Mummery C, Surti G, Hannequin D, Wallon D, Berman S, Lah J, Jiménez‐Velazquez I, Roberson E, van Dyck C, Honig L, Sanchez‐Valle R, Brooks W, Gauthier S, Masters C, Galasko D, Brosch J, Hsiung G, Jayadev S, Formaglio M, Masellis M, Clarnette R, Pariente J, Dubois B, Pasquier F, Andersen S, Holdridge K, Mintun M, Sims J, Yaari R, Team D. Solanezumab in‐depth outcomes. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.038028.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseDelayed Recall scoresAlzheimer's diseaseDisease progressionDouble-blind placebo-controlled trialLate-onset sporadic Alzheimer's diseaseTotal scoreLow-dose trialPlacebo-controlled trialAnti-amyloid therapiesOnset of symptomsPrimary cognitive outcome measureΒ-amyloid proteinInternational Shopping List TestMMSE total scoreDisease progression modelPrimary endpointSecondary outcomesSymptomatic patientsDose trialControl subjectsCSF markersClinical trialsCognitive outcome measuresEarly initiationBiochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex
Leslie S, Datta D, Wang M, van Dyck C, Arnsten A, Nairn A. Biochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.042017.Peer-Reviewed Original ResearchTau pathologyAge-related dysregulationAlzheimer's diseaseIntracellular calciumTau phosphorylationRhesus monkeysRat primary cortical culturesHuman post-mortem samplesVulnerable brain regionsSporadic Alzheimer's diseaseAmyloid-beta plaquesPrimary cortical culturesMain pathological hallmarksRhesus monkey cortexTau neurofibrillary tanglesYears of ageEarly-onset formAge-related vulnerabilityDorsolateral prefrontal cortexAge-related changesMonkey DLPFCPost-mortem samplesAD pathologyAmyloid pathologyUnknown etiologyGantenerumab in‐depth outcomes
Salloway S, Bateman R, Aschenbrenner A, Benzinger T, Clifford D, Coalier K, Cruchaga C, Fagan A, Farlow M, Goate A, Gordon B, Hassenstab J, Jack C, Koeppe R, McDade E, Mills S, Morris J, Santacruz A, Snyder P, Wang G, Xiong C, Snider B, Mummery C, Surti G, Hannequin D, Wallon D, Berman S, Lah J, Jiménez‐Velazquez I, Roberson E, van Dyck C, Honig L, Sanchez‐Valle R, Brooks W, Gauthier S, Masters C, Galasko D, Brosch J, Hsiung G, Jayadev S, Formaglio M, Masellis M, Clarnette R, Pariente J, Dubois B, Pasquier F, Baudler M, Delmar P, Doody R, Fontoura P, Kerchner G, Team D. Gantenerumab in‐depth outcomes. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.038049.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseAlzheimer's diseaseCognitive endpointsCDR-SBAmyloid PETBiomarker outcomesMutation carriersSecondary clinical outcomesSecondary efficacy endpointsAutosomal dominant Alzheimer's diseaseClinical trial programClinical Alzheimer's diseaseBeta monoclonal antibodySymptomatic Alzheimer's diseaseAnti-amyloid antibodiesCognitive compositeSymptomatic mutation carriersEfficacy endpointPlacebo groupPrimary outcomeClinical outcomesInitial doseFluid biomarkersTau-PETAmyloid reduction
2006
Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease
Zdanys KF, Kleiman TG, MacAvoy MG, Black BT, Rightmer TE, Grey M, Garman KS, Tampi RR, Gelernter J, van Dyck CH. Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease. Neuropsychopharmacology 2006, 32: 171-179. PMID: 16841077, DOI: 10.1038/sj.npp.1301148.Peer-Reviewed Original ResearchConceptsAD patientsPsychotic symptomsAlzheimer's diseaseBehavioral symptomsNeuropsychiatric InventoryApolipoprotein EMultiple logistic regression modelSporadic Alzheimer's diseaseGenetic risk factorsSevere-stage Alzheimer's diseaseLogistic regression modelsDifferent risk profilesDementia progressesRisk factorsIncrease riskBehavioral disturbancesPatientsDisease severitySymptomsSignificant psychosisRisk profileGreater riskApoEExploratory analysisDisease