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 labelingMonkeysStudies 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 mechanismBiochemical 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 etiologyMapping 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 labelingHypothesis: 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