2025
The neuropathologic basis for translational biomarker development in the macaque model of late-onset Alzheimer's disease.
Zeiss C, Huttner A, Nairn A, Arnsten A, Datta D, Strittmatter S, Wyk B, Duque A. The neuropathologic basis for translational biomarker development in the macaque model of late-onset Alzheimer's disease. Journal Of Alzheimer's Disease 2025, 13872877251323787. PMID: 40095666, DOI: 10.1177/13872877251323787.Peer-Reviewed Original ResearchAlzheimer's diseaseLate-onset Alzheimer's diseaseModel of late-onset Alzheimer's diseaseBraak stages III-IVDisruption of synaptic connectivityFormalin fixed paraffinAccumulation of senescence markersTau phosphorylationAmyloid-bFibrillar tauSenescence markersCo-morbiditiesPTau expressionLabile proteinBiomarker developmentStage III-IVSynaptic disruptionGlial fibrillary acidic proteinSenescence markers p16Fibrillary acidic proteinPredictive biomarkersFFPE tissuesMacaque modelAcidic proteinIII-IVSubcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease
Cai Y, Kanyo J, Wilson R, Bathla S, Cardozo P, Tong L, Qin S, Fuentes L, Pinheiro-de-Sousa I, Huynh T, Sun L, Mansuri M, Tian Z, Gan H, Braker A, Trinh H, Huttner A, Lam T, Petsalaki E, Brennand K, Nairn A, Grutzendler J. Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease. Nature Aging 2025, 5: 504-527. PMID: 40065072, PMCID: PMC11922768, DOI: 10.1038/s43587-025-00823-3.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProximity labeling approachIPSC-derived neuronsSubcellular proteomicsCytoskeleton dynamicsPhosphorylated mTOR levelsDystrophic neuritesLipid transportBiological processesProtein turnoverAD modelHuman induced pluripotent stem cellsAmyloid depositsIPSC modelsProteomicsInduced pluripotent stem cellsPluripotent stem cellsMTOR inhibitionTherapeutic targetAxonal pathologyLabeling approachMTOR levelsMouse brainSpheroid formationAlzheimer
2022
Alzheimer disease neuropathology in a patient previously treated with aducanumab
Plowey ED, Bussiere T, Rajagovindan R, Sebalusky J, Hamann S, von Hehn C, Castrillo-Viguera C, Sandrock A, Budd Haeberlein S, van Dyck CH, Huttner A. Alzheimer disease neuropathology in a patient previously treated with aducanumab. Acta Neuropathologica 2022, 144: 143-153. PMID: 35581440, PMCID: PMC9217863, DOI: 10.1007/s00401-022-02433-4.Peer-Reviewed Original ResearchConceptsAmyloid-related imaging abnormalitiesLong-term extensionStandard uptake value ratioAlzheimer's diseaseAmyloid positron emission tomographyBraak stage VPhase 1b studyPhospho-tau immunohistochemistryPostmortem neuropathologic examinationSpecies of AβAD neuropathologic changeFirst autopsy reportAlzheimer's disease neuropathologyUptake value ratioAmyloid PET scanMild Alzheimer's diseasePositron emission tomographyLast doseReactive microgliaNeuropathologic evidenceNeuropathologic examinationPlacebo armImaging abnormalitiesMonthly dosesNeuropathologic changes
2021
Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells
Franjic D, Skarica M, Ma S, Arellano JI, Tebbenkamp ATN, Choi J, Xu C, Li Q, Morozov YM, Andrijevic D, Vrselja Z, Spajic A, Santpere G, Li M, Zhang S, Liu Y, Spurrier J, Zhang L, Gudelj I, Rapan L, Takahashi H, Huttner A, Fan R, Strittmatter SM, Sousa AMM, Rakic P, Sestan N. Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron 2021, 110: 452-469.e14. PMID: 34798047, PMCID: PMC8813897, DOI: 10.1016/j.neuron.2021.10.036.Peer-Reviewed Original ResearchConceptsDisease-related proteinsCellular diversityCross-species analysisSingle-nucleus transcriptomesLipid droplet proteinsSpecies-specific propertiesImmature neuron populationTranscriptomic taxonomyAlzheimer's disease-related proteinsEndoplasmic reticulumCell typesHuman neuronsSpecies differencesHistologic signatureNeurogenic capabilityProteinExcitatory neuronsDiversityAdult miceGranule cellsAlzheimer's diseaseNeuron populationsCognitive functionEntorhinal cellsAdult humansSpreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-β
Nies SH, Takahashi H, Herber CS, Huttner A, Chase A, Strittmatter SM. Spreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-β. Journal Of Biological Chemistry 2021, 297: 101159. PMID: 34480901, PMCID: PMC8477193, DOI: 10.1016/j.jbc.2021.101159.Peer-Reviewed Original ResearchConceptsTau seedsAlzheimer's diseaseAD model miceWT mouse brainPathological tauSynaptic lossTau accumulationWT miceMouse tauTau pathologyTau burdenModel miceTau inclusionsPharmacological interventionsAD riskCognitive declineMouse brainTau aggregatesPyk2 kinaseKnowledge of factorsKinase inhibitorsMiceFyn kinase inhibitorAβMouse aging
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
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