2024
Synaptic density patterns in early Alzheimer’s disease assessed by independent component analysis
Fang X, Raval N, O’Dell R, Naganawa M, Mecca A, Chen M, van Dyck C, Carson R. Synaptic density patterns in early Alzheimer’s disease assessed by independent component analysis. Brain Communications 2024, 6: fcae107. PMID: 38601916, PMCID: PMC11004947, DOI: 10.1093/braincomms/fcae107.Peer-Reviewed Original ResearchMedial temporal brain regionsAlzheimer's diseaseTemporal brain regionsCognitive deficitsBrain regionsCognitive impairmentPostmortem studiesBinds to SV2ASynaptic densityReduction of synaptic densityIndependent component analysisSynaptic lossAlzheimerDeficitsImpairmentBrainNeocortexComponent analysisPrimary pathologySV2ASynaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 42. PMID: 38402233, PMCID: PMC10894197, DOI: 10.1038/s41531-024-00655-9.Peer-Reviewed Original ResearchSynaptic density lossPositron emission tomographyBinds to synaptic vesicle glycoprotein 2AAssociated with symptom severityParkinson's diseaseHigh-resolution positron emission tomographySynaptic vesicle glycoprotein 2ADuration of illnessPositron emission tomography scanBrain perfusionIllness durationSymptom severitySeverity of symptomsHC groupSubstantia nigraSynaptic densityLiving brainPD individualsClinical insightsDensity lossPD patientsEmission tomographyBrainSynaptic lossSynapse loss
2023
The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J
Toyonaga T, Khattar N, Wu Y, Lu Y, Naganawa M, Gallezot J, Matuskey D, Mecca A, Pittman B, Dias M, Nabulsi N, Finnema S, Chen M, Arnsten A, Radhakrishnan R, Skosnik P, D’Souza D, Esterlis I, Huang Y, van Dyck C, Carson R. The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 51: 1012-1022. PMID: 37955791, DOI: 10.1007/s00259-023-06487-8.Peer-Reviewed Original ResearchSynaptic densityAge-related decreaseMagnetic resonance imagingBlood flowAge-related synaptic lossGray matter volume lossSynaptic density lossPositron emission tomography (PET) ligandSynaptic vesicle glycoprotein 2AVivo PET measurementsMedial occipital cortexGray matter volumeAge-related neurodegenerationGray matter regionsCognitive normal subjectsAge-related changesSynaptic lossNerve terminalsWide age rangeOccipital cortexTomography ligandNormal subjectsGM volumeAge-related functional lossesMatter volume
2022
Imaging of Synaptic Density in Neurodegenerative Disorders
Carson RE, Naganawa M, Toyonaga T, Koohsari S, Yang Y, Chen MK, Matuskey D, Finnema SJ. Imaging of Synaptic Density in Neurodegenerative Disorders. Journal Of Nuclear Medicine 2022, 63: 60s-67s. PMID: 35649655, DOI: 10.2967/jnumed.121.263201.Peer-Reviewed Original ResearchConceptsSynaptic densityAlzheimer's diseaseNeurodegenerative disordersNeurodegenerative diseasesSynaptic vesicle protein 2APotential reference regionsSynaptic density lossLewy body dementiaProgressive supranuclear palsyDisease-modifying therapiesSpecific brain proteinsLarge patient cohortAntiepileptic drug levetiracetamPET imaging resultsMultiple neurodegenerative disordersSynaptic lossSupranuclear palsyCorticobasal degenerationNeuropathologic diseasePatient cohortRat modelClinical valueF-FDGParkinson's diseaseEfficacy assessment
2021
Association of Aβ deposition and regional synaptic density in early Alzheimer’s disease: a PET imaging study with [11C]UCB-J
O’Dell R, Mecca AP, Chen MK, Naganawa M, Toyonaga T, Lu Y, Godek TA, Harris JE, Bartlett HH, Banks ER, Kominek VL, Zhao W, Nabulsi NB, Ropchan J, Ye Y, Vander Wyk BC, Huang Y, Arnsten AFT, Carson RE, van Dyck CH. Association of Aβ deposition and regional synaptic density in early Alzheimer’s disease: a PET imaging study with [11C]UCB-J. Alzheimer's Research & Therapy 2021, 13: 11. PMID: 33402201, PMCID: PMC7786921, DOI: 10.1186/s13195-020-00742-y.Peer-Reviewed Original ResearchConceptsRegional Aβ depositionAβ depositionEarly Alzheimer's diseaseSynaptic lossSynaptic densityAlzheimer's diseaseDistribution volume ratioPositron emission tomographyHippocampal synaptic densityMild AD dementiaDeposition of AβSignificant inverse associationAmnestic mild cognitive impairmentWhole-brain analysisMild cognitive impairmentCerebellar reference regionPET imaging studiesPlaque burdenAD dementiaInverse associationPostmortem studiesClinical severityNeurodegenerative processesClinical diseaseLarge cohort
2020
In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET
Mecca AP, Chen M, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Nabulsi NB, Vander Wyk B, Varma P, Arnsten AFT, Huang Y, Carson RE, van Dyck C. In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET. Alzheimer's & Dementia 2020, 16: 974-982. PMID: 32400950, PMCID: PMC7383876, DOI: 10.1002/alz.12097.Peer-Reviewed Original ResearchConceptsWidespread synaptic lossEarly Alzheimer's diseaseSynaptic lossAlzheimer's diseaseSynaptic vesicle glycoprotein 2AGray matter volumeMajor structural correlatePositron emission tomography (PET) imagingEmission Tomography ImagingDistribution volume ratioCerebellar reference regionNeocortical brain regionsSynaptic densityAD progressionConsistent pathologyPotential therapyMatter volumePromising biomarkerCognitive impairmentCN participantsBrain regionsDiseaseTomography imagingNormal participantsStructural correlatesSynaptic Changes in Parkinson Disease Assessed with in vivo Imaging
Matuskey D, Tinaz S, Wilcox KC, Naganawa M, Toyonaga T, Dias M, Henry S, Pittman B, Ropchan J, Nabulsi N, Suridjan I, Comley RA, Huang Y, Finnema SJ, Carson RE. Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging. Annals Of Neurology 2020, 87: 329-338. PMID: 31953875, PMCID: PMC7065227, DOI: 10.1002/ana.25682.Peer-Reviewed Original ResearchConceptsSubstantia nigraParkinson's diseaseNormal controlsSynaptic changesPositron emission tomographic imagingSynaptic vesicle glycoprotein 2AParkinson's disease groupParkinson's disease subjectsEmission tomographic imagingPrimary brain areasAnn NeurolPostmortem autoradiographyBilateral diseaseNonmotor symptomsSynaptic lossNeuronal alterationsRelevant cortical areasStriatal dopamineBrainstem nucleiDisease groupDopamine neuronsLocus coeruleusCortical areasRed nucleusDopamine system
2019
Lower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
2018
Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging
Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurology 2018, 75: 1215-1224. PMID: 30014145, PMCID: PMC6233853, DOI: 10.1001/jamaneurol.2018.1836.Peer-Reviewed Original ResearchConceptsPositron emission tomographic imagingSynaptic vesicle glycoprotein 2ASynaptic densityAlzheimer's diseaseEmission tomographic imagingHigh-resolution PET scanningPET scanningCognitive impairmentDisease-modifying therapiesDisease-modifying treatmentsNormal participantsCross-sectional studyPittsburgh compound BMajor structural correlateAmnestic mild cognitive impairmentMagnetic resonance imagingMild cognitive impairmentJ PET imagingRestoration of synapsesSpecific bindingNeurologic evaluationSynaptic lossDisease stagePostmortem studiesOutcome measures