2024
Stress and inflammation target dorsolateral prefrontal cortex function: Neural mechanisms underlying weakened cognitive control
Joyce M, Uchendu S, Arnsten A. Stress and inflammation target dorsolateral prefrontal cortex function: Neural mechanisms underlying weakened cognitive control. Biological Psychiatry 2024 PMID: 38944141, DOI: 10.1016/j.biopsych.2024.06.016.Peer-Reviewed Original ResearchMental disordersDorsolateral prefrontal cortex functionPrefrontal cortex functionSubgenual cingulate cortexRegulate emotional responsesDorsolateral prefrontal cortexChronic stress exposurePosterior association cortexMedial PFCCognitive controlPrefrontal cortexWorking memoryCingulate cortexRegulate attentionCortex functionNeural mechanismsDlPFCBrain regionsStress exposureAssociation cortexTop-down projectionsEmotional responsesSpine lossArousal statePersistent firingThe circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex
Arnsten A, Martinez-Trujillo J. The circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex. 2024 DOI: 10.1016/b978-0-443-15754-7.00038-9.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexWorking memoryMechanisms of working memorySpatial working memoryPosterior association cortexExecutive functionMediodorsal thalamusSketch padMental representationsAssociation cortexSubcortical connectionsCholinergic neurotransmissionCircuit mechanismsRecurrent excitatory circuitsNMDA receptorsAbstract thoughtPersistent firingPrimate researchCortexDlPFCExcitatory circuitsMemorySensory stimulationAlzheimer's disease
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
2020
The 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 calcium
2019
Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease
Arnsten AFT, Datta D, Leslie S, Yang ST, Wang M, Nairn AC. Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 26230-26238. PMID: 31871209, PMCID: PMC6936707, DOI: 10.1073/pnas.1903671116.Peer-Reviewed Original ResearchTau pathologyAlzheimer's diseaseAssociation cortexTau phosphorylationMouse modelRhesus monkeysSignificant amyloid pathologyAlzheimer-like pathologyPrefrontal association cortexTau phosphorylation statePrimary sensory cortexOnset Alzheimer's diseasePrecursor protein cleavagePreventive therapyAmyloid pathologyCalcium dysregulationEarly stage degenerationPhosphorylated tauPrecipitating factorsSensory cortexCognitive deficitsAD researchRhesus macaquesPathologyCortexP4‐143: 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
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
2014
cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex
Carlyle BC, Nairn AC, Wang M, Yang Y, Jin LE, Simen AA, Ramos BP, Bordner KA, Craft GE, Davies P, Pletikos M, Šestan N, Arnsten AF, Paspalas CD. cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 5036-5041. PMID: 24707050, PMCID: PMC3977284, DOI: 10.1073/pnas.1322360111.Peer-Reviewed Original ResearchConceptsNeurofibrillary tanglesAssociation cortexAlzheimer's diseaseSpine apparatusPhosphorylated tauPattern of neurodegenerationLate-stage diseaseHigh-risk factorsNormal aged miceGenetic rodent modelsPrefrontal association cortexPrimary sensory cortexPrimary visual cortexAge-related increasePyramidal neuronsCorticocortical connectionsAged miceRisk factorsGlutamate synapsesSpine synapsesSelective vulnerabilityRodent modelsDendritic spinesSensory cortexProtein kinase phosphorylation
1997
The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer’s disease
van Dyck C, Lin C, Robinson R, Cellar J, Smith E, Nelson J, Arnsten A, Hoffer P. The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer’s disease. Psychopharmacology 1997, 132: 217-226. PMID: 9292621, DOI: 10.1007/s002130050339.Peer-Reviewed Original ResearchConceptsRegional cerebral blood flowParietal regional cerebral blood flowCerebral blood flowAlzheimer's diseaseAD patientsBlood flowDouble-blind trialWeeks of treatmentAD drug therapyProbable Alzheimer's diseaseParietal association cortexSingle photon emissionPlacebo TIDRCBF abnormalitiesCholinergic drugsDrug therapyHealthy controlsRCBF ratiosPharmacological interventionsHealthy subjectsAssociation cortexPatientsLinopirdineBrain regionsNeuropsychological function