2024
Nanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration
Datta D, Perone I, Wijegunawardana D, Liang F, Morozov Y, Arellano J, Duque A, Xie Z, van Dyck C, Joyce M, Arnsten A. Nanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration. Alzheimer's & Dementia 2024, 20: 2843-2860. PMID: 38445818, PMCID: PMC11032534, DOI: 10.1002/alz.13737.Peer-Reviewed Original Research
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 dysregulationLocalization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease
Datta D, Perone I, Morozov Y, Arellano J, Duque A, Rakic P, van Dyck C, Arnsten A. Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease. Cerebral Cortex 2023, 33: 11501-11516. PMID: 37874022, PMCID: PMC10724870, DOI: 10.1093/cercor/bhad382.Peer-Reviewed Original ResearchConceptsHCN1 channelsTau pathologyGlutamate synapsesEntorhinal cortexCalcium actionInternal calcium releaseEntorhinal cortex stellate cellsDorsolateral prefrontal cortexSusceptible neuronsInitial pathologySelective vulnerabilityEtiological factorsTau phosphorylationStellate cellsAlzheimer's diseaseSpecific neuronsCalcium releasePrefrontal cortexCortexSynapse strengthPathologyCalcium signalingCalbindinDiseaseNeurons557. Nanoscale Imaging of pT217-Tau in Aged Rhesus Macaque: Trans-Synaptic Propagation and Seeding of Tau Pathology in Entorhinal Cortex
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. 557. Nanoscale Imaging of pT217-Tau in Aged Rhesus Macaque: Trans-Synaptic Propagation and Seeding of Tau Pathology in Entorhinal Cortex. Biological Psychiatry 2023, 93: s319. DOI: 10.1016/j.biopsych.2023.02.797.Peer-Reviewed Original Research
2022
Nanoscale imaging of pT217‐tau in aged rhesus macaque: Trans‐synaptic propagation and seeding of tau pathology in entorhinal cortex
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Nanoscale imaging of pT217‐tau in aged rhesus macaque: Trans‐synaptic propagation and seeding of tau pathology in entorhinal cortex. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.064956.Peer-Reviewed Original ResearchTau pathologyAlzheimer's diseaseEntorhinal cortexCerebrospinal fluidLayers IIRhesus macaquesBrain tau pathologyHigher brain circuitsHigher cortical circuitsPattern of neurodegenerationAged rhesus macaquesHuman Alzheimer's diseaseTrans-synaptic propagationSoluble tau speciesSequence of tauAmyloid pathologyExtracellular spaceDendritic shaftsTau hyperphosphorylationGlutamatergic synapsesInhibitory synapsesNeurofibrillary tanglesSpine apparatusAD biomarkersEarly biomarkersSubcellular localization of PDE4D and HCN1 in rhesus macaque entorhinal cortex layer II: Signature of vulnerability in Alzheimer’s disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Subcellular localization of PDE4D and HCN1 in rhesus macaque entorhinal cortex layer II: Signature of vulnerability in Alzheimer’s disease. Alzheimer's & Dementia 2022, 17 DOI: 10.1002/alz.054671.Peer-Reviewed Original ResearchEntorhinal cortex layer IICortex layer IILayers IIAlzheimer's diseaseTau pathologySmooth endoplasmic reticulumPostsynaptic compartmentsPrefrontal cortexLayer II cellsLayer II stellate cellsDisease courseAsymmetric synapsesGlutamatergic circuitsDendritic shaftsCalcium dysregulationGlutamatergic synapsesSpine apparatusExcitatory synapsesCalcium leakAD subjectsDendritic spinesStellate cellsAssociation cortexCalcium extrusionSynaptic strength
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
Biochemical 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 etiology
2018
P3‐088: THE AGING RHESUS MONKEY IS AN APPROPRIATE NEW ANIMAL MODEL FOR STUDYING THE ETIOLOGY AND TREATMENT OF TAU PATHOLOGY IN ASSOCIATION CORTEX
Arnsten A, Carlyle B, Leslie S, Preuss T, Crimins J, Datta D, Anita H, van Dyck C, Rosene D, Nairn A, Paspalas C. P3‐088: THE AGING RHESUS MONKEY IS AN APPROPRIATE NEW ANIMAL MODEL FOR STUDYING THE ETIOLOGY AND TREATMENT OF TAU PATHOLOGY IN ASSOCIATION CORTEX. Alzheimer's & Dementia 2018, 14: p1099-p1099. DOI: 10.1016/j.jalz.2018.06.1444.Peer-Reviewed Original Research
2017
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas CD, Carlyle BC, Leslie S, Preuss TM, Crimins JL, Huttner AJ, van Dyck C, Rosene DL, Nairn AC, Arnsten AFT. The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology. Alzheimer's & Dementia 2017, 14: 680-691. PMID: 29241829, PMCID: PMC6178089, DOI: 10.1016/j.jalz.2017.11.005.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseCortical pathologyEntorhinal cortexAnimal modelsBraak stage III/IVAlzheimer's diseaseStage III/IVRhesus macaquesProgression of tauAlzheimer-like pathologyPrimary visual cortexSequence of tauDorsolateral prefrontal cortexTau pathologyPreventive strategiesAssociation cortexVisual cortexPrefrontal cortexCortexPathologyDiseaseOld animalsProtein kinase A (PKA) phosphorylationGenetic insultsMacaques