2025
Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation
Bathla S, Datta D, Bolat D, Woo E, Duque A, Arellano J, Arnsten A, Nairn A. Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation. Frontiers In Aging Neuroscience 2025, 17: 1549770. PMID: 40365352, PMCID: PMC12069431, DOI: 10.3389/fnagi.2025.1549770.Peer-Reviewed Original ResearchTau pathologyTau hyperphosphorylationAlzheimer's diseaseAssociated with tau hyperphosphorylationSoluble phosphorylated tauSporadic Alzheimer's diseaseCalcium signalingDysregulated calcium signalingTau etiologyEarly stages of ADHyperphosphorylationSignaling pathwayHuman ADInflammatory signaling pathwaysCalpain-2Stages of ADMolecular processesHydrolyze cAMPTauEntorhinal cortexCarboxypeptidase IIGlutamate carboxypeptidase IIDephosphorylationContrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices
Joyce M, Datta D, Arellano J, Duque A, Morozov Y, Morrison J, Arnsten A. Contrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices. Frontiers In Neuroanatomy 2025, 19: 1553056. PMID: 40255911, PMCID: PMC12006084, DOI: 10.3389/fnana.2025.1553056.Peer-Reviewed Original ResearchSubgenual cingulate cortexDorsolateral prefrontal cortexPrefrontal cortexPutative pyramidal neuronsN-methyl-D-aspartate receptorsN-methyl-D-aspartateSporadic Alzheimer's diseaseSubgenual cingulateCingulate cortexWorking memoryMacaque dlPFCDlPFCNMDAR antagonistsGluN2B subunitVulnerable to alterationsCortexSynaptic expressionPyramidal neuronsSynaptic functionAlzheimer's diseaseNeurodegenerative processesExtrasynaptic sitesTau pathologySchizophreniaCingulateThe etiology and prevention of early‐stage tau pathology in higher cortical circuits: Insights from aging rhesus macaques
Datta D, Arnsten A. The etiology and prevention of early‐stage tau pathology in higher cortical circuits: Insights from aging rhesus macaques. Alzheimer's & Dementia 2025, 21: e14477. PMID: 39776253, PMCID: PMC11848412, DOI: 10.1002/alz.14477.Peer-Reviewed Original ResearchConceptsAged macaquesAged rhesus macaquesP-tauTau hyperphosphorylationCortical circuitsAmyloid-beta generationSoluble phosphorylated tauCognitive deficitsAged monkeysSoluble hyperphosphorylated tauSporadic Alzheimer's diseaseAssociation cortexEarly-stage pathologyRhesus macaquesIncreased ABCalcium dysregulationCalcium regulationToxic to neuronsHyperphosphorylated tauAmyloid-betaCortexInflammatory signalingP-tau217 levelsTau pathologyPhosphorylated tau
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 dysregulationInterrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives
Datta D. Interrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives. The Journals Of Gerontology Series A 2023, 78: 1523-1534. PMID: 37279946, PMCID: PMC10460555, DOI: 10.1093/gerona/glad134.Peer-Reviewed Original ResearchConceptsPrimate dorsolateral prefrontal cortexSporadic Alzheimer's diseaseAlzheimer's diseaseDorsolateral prefrontal cortexRhesus macaquesPrefrontal cortexSignificant risk factorsHuman Alzheimer's diseaseAspartic acid (NMDA) receptorsNonhuman primate modelNovel therapeutic strategiesCalcium-buffering proteinsPattern of pathologyInflammatory cascadeTau pathologyNeuropathological cascadeSynaptic dysfunctionRisk factorsPrimate modelNeurofibrillary tanglesAmyloid plaquesDendritic spinesTherapeutic strategiesGenetic predispositionAnimal models
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 etiologyHypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease
Arnsten AFT, Datta D, Del Tredici K, Braak H. Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease. Alzheimer's & Dementia 2020, 17: 115-124. PMID: 33075193, PMCID: PMC7983919, DOI: 10.1002/alz.12192.Peer-Reviewed Original ResearchConceptsAbnormal tau phosphorylationTau pathologyProjection neuronsTau phosphorylationAssociation cortexAlzheimer's diseaseBrain tau pathologySporadic Alzheimer's diseaseSusceptible microenvironmentCalcium dysregulationVulnerable neuronsAβ plaquesAβ productionSporadic formsSAD pathologyRhesus monkeysAbnormal phosphorylationPathological eventsDiseaseAβ oligomersPathologyNeuronsVicious cycleCortexTau
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