2022
Subcellular 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
Studies of aging nonhuman primates illuminate the etiology of early‐stage Alzheimer's‐like neuropathology: An evolutionary perspective
Arnsten AFT, Datta D, Preuss TM. Studies of aging nonhuman primates illuminate the etiology of early‐stage Alzheimer's‐like neuropathology: An evolutionary perspective. American Journal Of Primatology 2021, 83: e23254. PMID: 33960505, PMCID: PMC8550995, DOI: 10.1002/ajp.23254.Peer-Reviewed Original ResearchConceptsTau pathologyAssociation cortexAlzheimer's diseaseTau phosphorylationNMDAR-NR2BRhesus monkeysCognitive deficitsMonkey dorsolateral prefrontal cortexAlzheimer-like neuropathologyInternal calcium releaseGenetic mouse modelsDorsolateral prefrontal cortexSynaptic lossNeurofibrillary tanglesAmyloid plaquesMouse modelEarly molecular eventsSporadic formsAutosomal dominant formCalcium releasePerfusion fixationCortexPrefrontal cortexNonhuman primatesPathology
2020
The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex
Arnsten AFT, Datta D, Wang M. The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex. Molecular Psychiatry 2020, 26: 3684-3700. PMID: 33319854, PMCID: PMC8203737, DOI: 10.1038/s41380-020-00973-3.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexCognitive disordersPrefrontal cortexPrimate dorsolateral prefrontal cortexHigher cortical circuitsPrimary visual cortexInternal calcium releaseRisk of schizophreniaAge-related lossLevels of calciumDendritic atrophyAmyloid pathologyCalcium binding proteinInflammatory insultCalcium overloadTau phosphorylationCortical circuitsDendritic spinesNeuronal firingCalcium channelsAssociation cortexSynaptic efficacyVisual cortexAlzheimer's diseaseSpecial molecular mechanismThe calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. The calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.047651.Peer-Reviewed Original ResearchLate-onset Alzheimer's diseaseAlzheimer's diseaseSmooth endoplasmic reticulumAD pathologyCalcium dysregulationRisk factorsCalcium leakMonkey dorsolateral prefrontal cortexAutosomal dominant Alzheimer's diseaseNeurofibrillary tangle formationGenetic risk factorsMedial temporal lobeDorsolateral prefrontal cortexMonkey DLPFCAD neurodegenerationTangle formationAge-related pathologiesTemporal lobeAnimal modelsAssociation cortexPS2 mutationTherapeutic interventionsBrain regionsEtiological eventInternal calciumMapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits
Datta D, Enwright JF, Arion D, Paspalas CD, Morozov YM, Lewis DA, Arnsten AFT. Mapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits. Frontiers In Neuroanatomy 2020, 14: 578483. PMID: 33328902, PMCID: PMC7714912, DOI: 10.3389/fnana.2020.578483.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexSmooth endoplasmic reticulumPrefrontal cortexHuman dlPFCPrimate dorsolateral prefrontal cortexHuman post-mortem tissueInternal calcium releasePrimate association corticesPost-mortem tissueMacaque dorsolateral prefrontal cortexPrimate dlPFCAxospinous synapsesPV interneuronsGlutamatergic connectionsGlutamatergic synapsesPyramidal cellsAxon terminalsTransmitter releaseTau phosphorylationDendritic spinesPDE4 isozymesAssociation cortexLayer IIICAMP actionPostsynaptic labelingPhosphodiesterase PDE4D Is Decreased in Frontal Cortex of Aged Rats and Positively Correlated With Working Memory Performance and Inversely Correlated With PKA Phosphorylation of Tau
Leslie SN, Datta D, Christensen KR, van Dyck CH, Arnsten AFT, Nairn AC. Phosphodiesterase PDE4D Is Decreased in Frontal Cortex of Aged Rats and Positively Correlated With Working Memory Performance and Inversely Correlated With PKA Phosphorylation of Tau. Frontiers In Aging Neuroscience 2020, 12: 576723. PMID: 33192469, PMCID: PMC7655962, DOI: 10.3389/fnagi.2020.576723.Peer-Reviewed Original ResearchFrontal association cortexAged ratsAlzheimer's diseaseAD tau pathologyAD-related sitesAge-related lossMemory-enhancing effectsLargest risk factorPhosphorylation of tauAge-related changesTau dissociationTau pathologyRisk factorsTau hyperphosphorylationFrontal cortexHealthy individualsTherapeutic targetAssociation cortexCognitive impairmentGEBR-7bBrain regionsRodent hippocampusPotassium channelsPhosphodiesterase 4DRatsHypothesis: 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
2019
P4‐143: LOSS OF PDE4D REGULATION OF CAMP‐PKA‐CALCIUM SIGNALING IN THE AGING ASSOCIATION CORTEX: INCREASING RISK FOR LOAD
Datta D, Morozov Y, Arellano J, van Dyck C, Arnsten A. P4‐143: LOSS OF PDE4D REGULATION OF CAMP‐PKA‐CALCIUM SIGNALING IN THE AGING ASSOCIATION CORTEX: INCREASING RISK FOR LOAD. Alzheimer's & Dementia 2019, 15: p1329-p1329. DOI: 10.1016/j.jalz.2019.06.3804.Peer-Reviewed Original Research
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