2025
The 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
2024
Diagnosis of Alzheimer’s disease‐ Analysis of cross‐species biomarkers
Bathla S. Diagnosis of Alzheimer’s disease‐ Analysis of cross‐species biomarkers. Alzheimer's & Dementia 2024, 20: e095406. PMCID: PMC11712473, DOI: 10.1002/alz.095406.Peer-Reviewed Original ResearchEntorhinal cortexAD patientsP-tauTau pathologyAged rhesus monkeysDKI miceQuantitative phospho-proteomicsPrefrontal cortexStages of ADAntibody-free methodAged monkeysMultifactorial neurodegenerative disorderChronic treatmentNon-human primatesAged rhesus macaquesMouse tauEnvironmental linksPhospho-proteomicsPhosphorylation sitesTau hyperphosphorylationRhesus monkeysP-tau181 concentrationsWestern blot analysisLumipulse platformCortexImmunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection
Cinco I, Napier E, Rhoades N, Davies M, Allison D, Kohama S, Bermudez L, Winthrop K, Fuss C, Spindel E, Messaoudi I. Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection. MBio 2024, 15: e00829-24. PMID: 38771046, PMCID: PMC11237422, DOI: 10.1128/mbio.00829-24.Peer-Reviewed Original ResearchConceptsNTM pulmonary diseaseIncreased disease severityNontuberculous mycobacteriaDisease severityBacterial DNAAged animalsAntigen-specific T cellsPulmonary diseaseAssociated with increased disease severityDysregulated macrophage responsePersistence of bacterial DNALack of animal modelsRhesus macaquesSingle-cell RNA sequencingNontuberculous mycobacterial infectionsImmune cell infiltrationRhesus macaque modelBacterial loadAged rhesus macaquesTesting novel therapeuticsRight caudal lobeLower respiratory microbiomeYears of ageMAH infectionMicrobial communities
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 dysregulation557. 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 biomarkers
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