2025
Glucagon-like Peptide-1 receptor agonists for the prevention and treatment of Parkinson’s disease
Lee S, Yin L, Xiao N, Rhee T, Lo H, Wong S, Fox S, Teopiz K, Lam B, Zheng Y, Le G, Mansur R, Rosenblat J, McIntyre R. Glucagon-like Peptide-1 receptor agonists for the prevention and treatment of Parkinson’s disease. CNS Spectrums 2025, 30: e44. PMID: 40485141, DOI: 10.1017/s109285292510031x.Peer-Reviewed Original ResearchConceptsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsGLP-1RAsCentral nervous systemReceptor agonistsEvidence of clinically meaningful benefitFood and Drug Administration (FDA)-approved treatmentsTreatment-emergent adverse eventsParkinson's diseaseEffects of GLP-1RAsEmergent adverse eventsClinically meaningful benefitFDA-approved treatmentClinical trial evidenceNo current therapyTreatment of Parkinson's diseasePreclinical evidenceAdverse eventsCurrent therapiesMeaningful benefitClinical evidenceFeatures of PDTherapeutic benefitTrial evidenceInsulin resistanceReduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease
Abulimiti A, Bae H, Ali A, Balakrishnan S, Tsujishita M, Gveric D, Tierney T, Jonas E, Smith P, Gentleman S, Alavian K. Reduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease. Science Advances 2025, 11: eads3051. PMID: 40479058, PMCID: PMC12143374, DOI: 10.1126/sciadv.ads3051.Peer-Reviewed Original ResearchConceptsProximity ligation assayVentral tegmental areaF1Fo-ATP synthaseProximity ligation assay signalsMetabolic efficiencyVentral tegmental area neuronsMitochondrial metabolic efficiencyProtein productionLigation assayMitochondrial activityMetabolic homeostasisIntracellular compartmentsMitochondrial efficiencyDistal neuritesParkinson's diseaseControl postmortem brainsImpaired mitochondrial efficiencySubstantia nigra pars compactaDopaminergic neuron vulnerabilityMesDA neuronsMesencephalic dopaminergicNeuronal vulnerabilityTegmental areaNeuronal subpopulationsIdiopathic Parkinson's diseaseSocioeconomic area deprivation and its relationship with dementia, Parkinson's Disease and all-cause mortality among UK older adults: a multistate modeling approach
Beydoun M, Georgescu M, Weiss J, Noren Hooten N, Beydoun H, Tsai J, Maino Vieytes C, Evans M, Zonderman A. Socioeconomic area deprivation and its relationship with dementia, Parkinson's Disease and all-cause mortality among UK older adults: a multistate modeling approach. Social Science & Medicine 2025, 379: 118137. PMID: 40388863, DOI: 10.1016/j.socscimed.2025.118137.Peer-Reviewed Original ResearchConceptsArea-level deprivationTownsend deprivation indexSocioeconomic statusCardiovascular healthArea-level socioeconomic statusUK older adultsAll-cause mortalityDementia deathsArea deprivationDeprivation indexUK BiobankCox proportional hazardsOlder adultsDementiaParkinson's diseasePD dementiaPotential mediatorsZ-scoreProportional hazardsMultistate modeling approachHealthMortalityMultistate modelWeibull regressionMultistate approachParkinson’s disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction
Wilson E, Umans J, Swarovski M, Minhas P, Mendiola J, Midttun Ø, Ulvik A, Shahid-Besanti M, Linortner P, Mhatre S, Wang Q, Channappa D, Corso N, Tian L, Fredericks C, Kerchner G, Plowey E, Cholerton B, Ueland P, Zabetian C, Gray N, Quinn J, Montine T, Sha S, Longo F, Wolk D, Chen-Plotkin A, Henderson V, Wyss-Coray T, Wagner A, Mormino E, Aghaeepour N, Poston K, Andreasson K. Parkinson’s disease is characterized by vitamin B6-dependent inflammatory kynurenine pathway dysfunction. Npj Parkinson's Disease 2025, 11: 96. PMID: 40287426, PMCID: PMC12033312, DOI: 10.1038/s41531-025-00964-7.Peer-Reviewed Original ResearchCerebral spinal fluidKynurenine pathwayKynurenic acidQuinolinic acidSites of brainB-vitamin statusParkinson's diseasePD clinical featuresVitamin B6 deficiencyKP metabolitesClinical featuresClinical manifestationsCerebral inflammationClinical symptomsPatient subgroupsB6 deficiencySpinal fluidPathway dysfunctionKynurenineCompare bloodDiseaseInflammationVitaminIncreased QASoluble TREM2Longitudinal Assessment of Parkinson’s Motor Symptoms and Dopaminergic Dysfunction Patterns Using DaTSCAN
Najmi A, Ariaei A, Khezri M, Noroozi M, Bafrani M, Gheysari A, Sabetghadam F, Ahmadi M, Sadeghi M, Mayeli M, Initiative T. Longitudinal Assessment of Parkinson’s Motor Symptoms and Dopaminergic Dysfunction Patterns Using DaTSCAN. Clinical Parkinsonism & Related Disorders 2025, 12: 100331. PMID: 40329978, PMCID: PMC12054110, DOI: 10.1016/j.prdoa.2025.100331.Peer-Reviewed Original ResearchPostural instabilityActivities of Daily Living (ADLMDS-UPDRSSymptom assessment scoresOrdinal logistic regression modelLogistic regression modelsTremor-dominantTwo-year follow-upParkinson's motor symptomsDisease severityClinical motor scoresEngland ActivitiesDifficulty scoreMotor scoresGait disturbanceSymptom severity trajectoriesDopamine transporter scanParkinson's diseaseMotor functionOverall disease severityDiagnosis of PDRegression modelsDaTSCAN findingsAssessment scoresSymptom patternsPolypharmacy and its association with dementia, Parkinson’s disease, and mortality risk in UK adults: a multistate modeling approach
Weiss J, Beydoun M, Georgescu M, Maldonado A, Beydoun H, Noren Hooten N, Tsai J, Song M, Nieva A, Evans M, Zonderman A. Polypharmacy and its association with dementia, Parkinson’s disease, and mortality risk in UK adults: a multistate modeling approach. GeroScience 2025, 47: 4349-4367. PMID: 40080299, PMCID: PMC12181516, DOI: 10.1007/s11357-025-01586-w.Peer-Reviewed Original ResearchConceptsHealth transitionOlder adultsCardiovascular healthLatent class analysisUK Biobank participantsRisks associated with polypharmacyHealth statesAssociated with dementiaPopulation-based cohortAssociated with higher riskYears of follow-upMedication combinationsClass analysisBiobank participantsHealth outcomesPolypharmacy statusPolypharmacy prevalenceSocioeconomic statusUK adultsMortality riskDementiaParkinson's diseasePolypharmacyHealthAdverse outcomesMicrostructural patterns in substantia nigra subregions are associated with depression and olfactory impairments in Parkinson’s disease
Mozafar M, Manshadi Z, Molaei Z, Babaei H, Mansouri M, Shahbazi S, Shakeri S, Mirhosseini H, Gulisashvili D, Mayeli M, Initiative P. Microstructural patterns in substantia nigra subregions are associated with depression and olfactory impairments in Parkinson’s disease. Clinical Neurology And Neurosurgery 2025, 251: 108817. PMID: 40080943, DOI: 10.1016/j.clineuro.2025.108817.Peer-Reviewed Original ResearchConceptsDiffusion tensor imagingNon-motor symptomsDopaminergic deficitOlfactory dysfunctionHealthy controlsSubstantia nigraPD patientsParkinson's diseaseDiffusion tensor imaging findingsAssociated with depressionRates of depressionHigher rates of depressionNon-motor testsEvidence of dopaminergic deficitNon-depressed onesOlfactory impairmentAnxiety scoresPrevalence of olfactory dysfunctionDepressionSWEDD groupTensor imagingPPMI databaseDeficitsFA valuesSWEDDCorrecting SUVR bias by accounting for radiotracer clearance in tissue: A validation study with [18F]FE-PE2I PET in cross-sectional, test-retest and longitudinal cohorts
Oh M, Honhar P, Carson R, Hillmer A, Varrone A. Correcting SUVR bias by accounting for radiotracer clearance in tissue: A validation study with [18F]FE-PE2I PET in cross-sectional, test-retest and longitudinal cohorts. Cerebrovascular And Brain Metabolism Reviews 2025, 45: 1357-1370. PMID: 39981611, PMCID: PMC11846093, DOI: 10.1177/0271678x251322407.Peer-Reviewed Original ResearchLRRK2, lysosome damage, and Parkinson's disease
Bentley-DeSousa A, Clegg D, Ferguson S. LRRK2, lysosome damage, and Parkinson's disease. Current Opinion In Cell Biology 2025, 93: 102482. PMID: 39983584, DOI: 10.1016/j.ceb.2025.102482.Peer-Reviewed Original ResearchConceptsLRRK2 kinase activityKinase activitySubstrate of LRRK2Rab familySmall GTPasesLysosomal biologyDamaged lysosomesEndolysosomal membranesRegulatory mechanismsNormal biologyPathogenesis of Parkinson's diseaseLRRK2Repair mechanismsLysosomal damageLysosomesBiologyGTPaseParkinson's diseaseRabGABARAPActivityCCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models
Leser F, Júnyor F, Pagnoncelli I, Delgado A, Medeiros I, Nóbrega A, Andrade B, de Lima M, da Silva N, Jacob L, Boyé K, Geraldo L, de Souza A, Maron-Gutierrez T, Castro-Faria-Neto H, Follmer C, Braga C, Neves G, Eichmann A, Romão L, Lima F. CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models. Journal Of Neuroinflammation 2025, 22: 31. PMID: 39894839, PMCID: PMC11789347, DOI: 10.1186/s12974-024-03318-x.Peer-Reviewed Original ResearchConceptsMouse model of PDModel of PDMouse modelDopaminergic neuronsNeuron-microglia communicationNeuron-glia communicationParkinson's diseaseCCR7-dependent mannerMicroglial cell activationCCR7 expressionCCL21-CCR7Progressive degenerative diseaseCCR7 receptorMicroglial cell migrationInflammatory profileChemokine CCL21Cell activationCCL21Therapeutic strategiesChemokine inhibitorsTherapeutic implicationsMicroglial activationReceptor pathwayCCR7Behavioral deficitsEvidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional study
Marek K, Russell D, Concha-Marambio L, Choi S, Jennings D, Brumm M, Coffey C, Brown E, Seibyl J, Stern M, Soto C, Siderowf A. Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional study. EBioMedicine 2025, 112: 105567. PMID: 39893720, PMCID: PMC11835612, DOI: 10.1016/j.ebiom.2025.105567.Peer-Reviewed Original ResearchConceptsDementia with Lewy bodiesCross-sectional studyCognitive symptomsParkinson Associated Risk Syndrome StudyPrevention StudyYear follow-upOlder individualsDopamine transporter imagingHigh riskSyndrome studiesParticipantsParkinson's diseaseHyposmic individualsFollow-upSynuclein pathologySymptomsHyposmicsDepartment of DefenseU.S. Department of DefenseIndividualsRiskLewy bodiesClinical parkinsonismMichael J. Fox FoundationDementiaRadiological markers of CSF α-synuclein aggregation in Parkinson’s disease patients
Droby A, Yoffe-Vasiliev A, Atias D, Fraser K, Mabrouk O, Omer N, Bar-Shira A, Gana-Weisz M, Goldstein O, Artzi M, Ben Bashat D, Alcalay R, Orr-Urtreger A, Shirvan J, Cedarbaum J, Giladi N, Mirelman A, Thaler A. Radiological markers of CSF α-synuclein aggregation in Parkinson’s disease patients. Npj Parkinson's Disease 2025, 11: 7. PMID: 39753572, PMCID: PMC11698941, DOI: 10.1038/s41531-024-00854-4.Peer-Reviewed Original ResearchStriatal binding ratiosLRRK2-PD patientsFunctional connectivityLeft fronto-occipital fasciculusCerebrospinal fluidGray matter volumeDeep gray matter volumesRegional brain volumesWhole-brain gray matterNeuromelanin MRIFronto-occipital fasciculusLRRK2-PDWhite matterParkinson's diseaseLeft caudateMatter volumeReduced FCParkinson's disease patientsWhole-brainBrain volumeRadiological markersHealthy controlsFractional anisotropyRadiological measurementsPatients
2024
Transcranial optogenetic brain modulator for precise bimodal neuromodulation in multiple brain regions
Shin H, Nam M, Lee S, Yang S, Yang E, Jung J, Kim H, Woo J, Cho Y, Yoon Y, Cho I. Transcranial optogenetic brain modulator for precise bimodal neuromodulation in multiple brain regions. Nature Communications 2024, 15: 10423. PMID: 39613730, PMCID: PMC11607408, DOI: 10.1038/s41467-024-54759-0.Peer-Reviewed Original ResearchConceptsBrain regionsBrain modulesModulation of brain functionTranscranial brain stimulationMultiple brain regionsUpconversion particlesSymptoms of Parkinson's diseaseOptical crosstalkStudy of neural circuitsFood competition testBrain dysfunctionExternal light sourceLight sourcesBrain functionStudy of complex behaviorsSpatial resolutionNeural circuitsBrain disordersDevelopment of treatmentsOptogenetic techniquesBrain stimulationNeural populationsBrainParkinson's diseaseNeuromodulationQuantification of cinpanemab (BIIB054) binding to α-synuclein in cerebrospinal fluid of phase 1 single ascending dose samples
Liu Y, Yang M, Fraser K, Graham D, Weinreb P, Weihofen A, Hirst W, Cedarbaum J, Pepinsky B. Quantification of cinpanemab (BIIB054) binding to α-synuclein in cerebrospinal fluid of phase 1 single ascending dose samples. Journal Of Pharmacology And Experimental Therapeutics 2024, 392: 100003. PMID: 39892989, DOI: 10.1124/jpet.124.002199.Peer-Reviewed Original ResearchCentral nervous systemCerebrospinal fluidMeso Scale DiscoveryCentral nervous system compartmentDrug concentrationsA-synCerebrospinal fluid samplesParkinson's diseasePassive immunotherapy approachesSite of actionImmunotherapy approachesLow drug concentrationsImmunotherapy trialsHealthy volunteersSystemic compartmentDrug-target interactionsCSF samplesObserved doseNervous systemTherapeutic targetA-syn levelsClinical samplesTime-dependent bindingComplex formationCross-linking methodPresynaptic terminal integrity is associated with glucose metabolism in Parkinson’s disease
Wang W, Wang Y, Xu L, Liu X, Hu Y, Li J, Huang Q, Ren S, Huang Y, Guan Y, Li Y, Hua F, Ye Q, Xie F. Presynaptic terminal integrity is associated with glucose metabolism in Parkinson’s disease. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 52: 1510-1519. PMID: 39572432, DOI: 10.1007/s00259-024-06993-3.Peer-Reviewed Original ResearchPositron emission tomographyDopamine transporterSynaptic densityGlucose metabolismDopamine transporter availabilityPD patientsPost-commissural caudateParkinson's diseaseReduced synaptic densityAssociated with glucose metabolismDopaminergic transporterMethodsA totalHealthy controlsSynaptic vesicle protein 2PatientsEmission tomographyCaudatePD groupMetabolic patternsTerminal integrityProtein 2DiseaseNC groupCaudate regionsMetabolismNeuroimaging Biomarkers in Parkinson’s Disease
Holmes S, Tinaz S. Neuroimaging Biomarkers in Parkinson’s Disease. Advances In Neurobiology 2024, 40: 617-663. PMID: 39562459, DOI: 10.1007/978-3-031-69491-2_21.Peer-Reviewed Original ResearchConceptsPublic health burdenNeuroimaging biomarkersTreatment developmentRisk of developing PDParkinson's diseaseHealth burdenDiagnosis of PDMultimodal neuroimaging techniquesIdiopathic Parkinson's diseaseNon-motorDifferential diagnosis of PDNeuroimaging techniquesProdromal phaseDifferential diagnosisSymptomatic treatmentDisease progressionClinical applicationBiomarkersSingle-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerabilityGlottal Insufficiency and Parkinson’s Disease: A Scoping Review of Vocal Fold Medialization Procedures
Garabedian M, Keltz A, Lerner M, Brackett A, Leydon C. Glottal Insufficiency and Parkinson’s Disease: A Scoping Review of Vocal Fold Medialization Procedures. Journal Of Voice 2024 PMID: 39438169, DOI: 10.1016/j.jvoice.2024.09.034.Peer-Reviewed Original Research In PressImprove vocal functionJoanna Briggs Institute checklistDiagnosis of participantsGrey literature resourcesProspective research designEnrollment of participantsQuality of lifeDebilitating symptom of Parkinson's diseaseScoping reviewInstitute checklistEnglish-language publicationsGeneralizability of findingsParticipant demographicsQuality of research articlesOutcome measuresAuditory-perceptualParkinson's diseaseEligibility criteriaInclusionary criteriaBiomedical databasesControl participantsSpeech therapyDebilitating symptomsPwPDVocal functionValidating new symptom emergence as a patient-centric outcome measure for PD clinical trials
Zou H, Stebbins G, Simuni T, Luo S, Cedarbaum J. Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials. Parkinsonism & Related Disorders 2024, 128: 107118. PMID: 39353265, DOI: 10.1016/j.parkreldis.2024.107118.Peer-Reviewed Original ResearchPD clinical trialsClinical trialsEmergent symptomsPhase 3 clinical trialsPhase 3 studySlowing of disease progressionOutcome measuresParkinson's diseaseDe novo Parkinson's diseaseMDS-UPDRSItem-level dataFrequency of ESSymptomatic medicationsFrequent administrationMonths of observationEfficacy assessmentDisease progressionSymptom emergenceRating ScaleItem responsesIb and IIUrate elevationTrialsSocioenvironmental Factors are Associated With Dopamine Transporter Availability in Healthy Individuals but not in Parkinson’s Disease
Cayir S, Tezel M, Matuskey D. Socioenvironmental Factors are Associated With Dopamine Transporter Availability in Healthy Individuals but not in Parkinson’s Disease. Journal Of Geriatric Psychiatry And Neurology 2024, 38: 143-149. PMID: 39244698, DOI: 10.1177/08919887241281062.Peer-Reviewed Original ResearchMedian household incomeDopaminergic functionHealthy individualsSocioenvironmental factorsEducation levelHousehold incomeZIP Code Tabulation AreasBrain dopaminergic functionDopamine transporter availabilityResidential zip codeParkinson's Progression Markers InitiativeParkinson's diseaseNo significant associationAmerican Community SurveyDAT availabilityDopamine transporterZip codesClinical dataHealthy subjectsSocioenvironmental variablesCommunity SurveySignificant associationPD groupPoverty ratesStudy findings
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