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 dysregulationLocalization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease
Datta D, Perone I, Morozov Y, Arellano J, Duque A, Rakic P, van Dyck C, Arnsten A. Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease. Cerebral Cortex 2023, 33: 11501-11516. PMID: 37874022, PMCID: PMC10724870, DOI: 10.1093/cercor/bhad382.Peer-Reviewed Original ResearchConceptsHCN1 channelsTau pathologyGlutamate synapsesEntorhinal cortexCalcium actionInternal calcium releaseEntorhinal cortex stellate cellsDorsolateral prefrontal cortexSusceptible neuronsInitial pathologySelective vulnerabilityEtiological factorsTau phosphorylationStellate cellsAlzheimer's diseaseSpecific neuronsCalcium releasePrefrontal cortexCortexSynapse strengthPathologyCalcium signalingCalbindinDiseaseNeurons557. 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
2020
PET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex
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