2025
Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease
Mecca A, Ashton N, Chen M, O'Dell R, Toyonaga T, Zhao W, Young J, Salardini E, Bates K, Ra J, Goodcase S, Silva‐Rudberg J, Nabulsi N, Brinkmalm A, Kvartsberg H, Schöll M, Nilsson J, Arnsten A, Huang Y, Hansson O, Zetterberg H, Carson R, Blennow K, van Dyck C. Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease. Alzheimer's & Dementia 2025, 21: e70344. PMID: 40491249, PMCID: PMC12149441, DOI: 10.1002/alz.70344.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2APositron emission tomographyAlzheimer's diseaseSynaptic densityEnzyme-linked immunosorbent assayC]UCB-J positron emission tomographyPositron emission tomography measurementsEmission tomographyAxonal proteinsCN participantsImmunosorbent assaySymptomatic Alzheimer's diseaseAD groupProteinAssayParticipantsSV2AAlzheimerCerebrospinal fluidBrainInvestigate associationsCerebrospinal fluid assaysSV2A positron emission tomographyAssessment of the relationship between synaptic density and metabotropic glutamate receptors in early Alzheimer’s disease: a multi-tracer PET study
Salardini E, O’Dell R, Tchorz E, Nabulsi N, Huang Y, Carson R, van Dyck C, Mecca A. Assessment of the relationship between synaptic density and metabotropic glutamate receptors in early Alzheimer’s disease: a multi-tracer PET study. Alzheimer's Research & Therapy 2025, 17: 98. PMID: 40329311, PMCID: PMC12054321, DOI: 10.1186/s13195-025-01739-1.Peer-Reviewed Original ResearchConceptsDistribution volume ratioMedial temporal lobePositron emission tomographyTemporal lobeSynaptic densityMetabotropic glutamate receptor subtype 5Multi-tracer PET studiesAlzheimer's diseaseCerebellum reference regionAmyloid-positive participantsSynaptic lossSynaptic vesicle glycoprotein 2AMetabotropic glutamate receptorsPositron emission tomography scanNeocortical regionsSubtype 5MGluR5Entorhinal cortexAD groupReference regionGlutamate receptorsExploratory analysisWidespread reductionsLongitudinal studyReceptor bindingGenerating synthetic brain PET images of synaptic density based on MR T1 images using deep learning
Zheng X, Worhunsky P, Liu Q, Guo X, Chen X, Sun H, Zhang J, Toyonaga T, Mecca A, O’Dell R, van Dyck C, Angarita G, Cosgrove K, D’Souza D, Matuskey D, Esterlis I, Carson R, Radhakrishnan R, Liu C. Generating synthetic brain PET images of synaptic density based on MR T1 images using deep learning. EJNMMI Physics 2025, 12: 30. PMID: 40163154, PMCID: PMC11958861, DOI: 10.1186/s40658-025-00744-5.Peer-Reviewed Original ResearchCannabis use disorderStructural similarity indexPET imagingImages of higher qualityMR-T1 imagesMean square errorUse disorderEncoder-decoderDeep learningCross-validation processData-driven approachDiagnostic categoriesLow-dose scansPredicted imageTemporal regionsBrain disordersGround truthT1-weighted MRISynaptic densityHuman brainSimilarity indexDisordersSevere neurological disordersTranslation accuracyNoise reduction
2024
Connectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease
de Bruin H, Groot C, ADNI, Barthel H, Bischof G, Boellaard R, Brendel M, Cash D, Coath W, Day G, Dickerson B, Doering E, Drzezga A, van Dyck C, van Eimeren T, van der Flier W, Fredericks C, Fryer T, van de Giessen E, Gordon B, Graff‐Radford J, Hobbs D, Höglinger G, Hönig M, Irwin D, Jones P, Josephs K, Katsumi Y, Lee E, Levin J, Malpetti M, McGinnis S, Mecca A, Nasrallah I, O'Brien J, O'Dell R, Palleis C, Perneczky R, Phillips J, Pijnenburg Y, Putcha D, Rahmouni N, Rosa‐Neto P, Rowe J, Rullmann M, Sabri O, Saur D, Schildan A, Schott J, Schroeter M, Servaes S, Sintini I, Stevenson J, Therriault J, Touroutoglou A, Trainer A, Visser D, Weston P, Whitwell J, Wolk D, Franzmeier N, Ossenkoppele R. Connectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease. Alzheimer's & Dementia 2024, 20: e085869. PMCID: PMC11714601, DOI: 10.1002/alz.085869.Peer-Reviewed Original ResearchAlzheimer's diseaseTau spreadingProgression of Alzheimer's diseaseTau-PETFunctional proximityPosterior patterningAD variantsTauPersonalized medicineTau-PET standardized uptake value ratiosVariantsWidespread patternAtypical ADDominant patternAtypical Alzheimer's diseaseRegionNeurodegenerationPositive probabilityPatternsConnectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease
de Bruin H, Groot C, ADNI, Barthel H, Bischof G, Boellaard R, Brendel M, Cash D, Coath W, Day G, Dickerson B, Doering E, Drzezga A, van Dyck C, van Eimeren T, van der Flier W, Fredericks C, Fryer T, van de Giessen E, Gordon B, Graff‐Radford J, Hobbs D, Höglinger G, Hönig M, Irwin D, Jones P, Josephs K, Katsumi Y, Lee E, Levin J, Malpetti M, McGinnis S, Mecca A, Nasrallah I, O'Brien J, O'Dell R, Palleis C, Perneczky R, Phillips J, Pijnenburg Y, Putcha D, Rahmouni N, Rosa‐Neto P, Rowe J, Rullmann M, Sabri O, Saur D, Schildan A, Schott J, Schroeter M, Servaes S, Sintini I, Stevenson J, Therriault J, Touroutoglou A, Trainer A, Visser D, Weston P, Whitwell J, Wolk D, Franzmeier N, Ossenkoppele R. Connectivity as a universal predictor of tau spreading in typical and atypical Alzheimer’s disease. Alzheimer's & Dementia 2024, 20: e093663. PMCID: PMC11713789, DOI: 10.1002/alz.093663.Peer-Reviewed Original ResearchAlzheimer's diseaseTau spreadingProgression of Alzheimer's diseaseTau-PETFunctional proximityPosterior patterningAD variantsTauPersonalized medicineTau-PET standardized uptake value ratiosVariantsWidespread patternAtypical ADDominant patternAtypical Alzheimer's diseaseRegionNeurodegenerationPatternsSelf‐reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort
Miller A, Sharp E, Wang S, Zhao Y, Mecca A, van Dyck C, O'Dell R, Initiative F. Self‐reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort. Alzheimer's & Dementia 2024, 20: 7847-7858. PMID: 39324520, PMCID: PMC11567835, DOI: 10.1002/alz.14252.Peer-Reviewed Original ResearchSelf-reported hearing lossFunctional Activities QuestionnaireHearing lossMild cognitive impairmentModifiable risk factorsMild cognitive impairment participantsFunctional declineImpairment diagnosisModified Preclinical Alzheimer Cognitive CompositeRate of functional declineRate of cognitive declinePreclinical Alzheimer Cognitive CompositeRisk factorsCognitive impairmentSignificant longitudinal associationsActivity QuestionnaireLongitudinal associationsAlzheimer's Disease Neuroimaging InitiativeLongitudinal relationshipCognitive compositeCN participantsIncreased riskCognitive declineParticipantsDiagnostic conversionValidation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET
Young J, O’Dell R, Naganawa M, Toyonaga T, Chen M, Nabulsi N, Huang Y, Cooper E, Miller A, Lam J, Bates K, Ruan A, Nelsen K, Salardini E, Carson R, van Dyck C, Mecca A. Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET. Journal Of Nuclear Medicine 2024, 65: jnumed.124.267419. PMID: 39299782, PMCID: PMC11533916, DOI: 10.2967/jnumed.124.267419.Peer-Reviewed Original ResearchDistribution volume ratioSUV ratioSynaptic densityEffect sizeAlzheimer's diseaseLongitudinal study of Alzheimer's diseaseMethods:</b> ParticipantsLongitudinal studyMeasure synaptic densityAD participantsStudy of Alzheimer's diseaseNormal cognitionReference regionOlder adultsMulticenterDensity alterationsCommentary on “Study Partner Report of Apathy in Older Adults is Associated With AD Biomarkers: Findings From the Harvard Aging Brain Study”
Khasnavis S, O'Dell R, van Dyck C, Mecca A. Commentary on “Study Partner Report of Apathy in Older Adults is Associated With AD Biomarkers: Findings From the Harvard Aging Brain Study”. American Journal Of Geriatric Psychiatry 2024, 32: 920-921. PMID: 38658231, DOI: 10.1016/j.jagp.2024.03.017.Peer-Reviewed Original ResearchSynaptic 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 pathologySV2AAssessment of disparities in timely diagnosis and comprehensive workup of cognitive impairment between English and Spanish speakers
Silva-Rudberg J, Carrión C, Pérez-Palmer N, Li J, Mehta S, Diab N, Mecca A, O'Dell R. Assessment of disparities in timely diagnosis and comprehensive workup of cognitive impairment between English and Spanish speakers. American Journal Of Geriatric Psychiatry 2024, 32: 773-786. PMID: 38336573, PMCID: PMC11162952, DOI: 10.1016/j.jagp.2024.01.030.Peer-Reviewed Original ResearchDiagnosis of mild cognitive impairmentSpanish-speaking patientsMild cognitive impairmentHispanic/Latino patientsCognitive impairmentNon-English language preferenceLanguage preferenceComprehension of diagnosisImpact of language barriersAssessment of disparitiesDiagnosis of cognitive impairmentSpanish language preferenceDiagnosis of dementiaElectronic medical recordsCross-sectional studyTimeliness of diagnosisDementia careRetrospective cross-sectional studyDementia diagnosisHealth disparitiesU.S. Hispanic/Latino populationBinomial logistic regressionNeighborhood disadvantageSpanish speakersHealth careA pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease
van Dyck C, Mecca A, O’Dell R, Bartlett H, Diepenbrock N, Huang Y, Hamby M, Grundman M, Catalano S, Caggiano A, Carson R. A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 20. PMID: 38273408, PMCID: PMC10809445, DOI: 10.1186/s13195-024-01382-2.Peer-Reviewed Original ResearchConceptsMild to moderate dementiaPositron emission tomographyAlzheimer's diseaseVolumetric MRIModerate dementiaClinical rating scalesSynaptic vesicle glycoprotein 2ACerebrospinal fluidMouse model of ADPharmacodynamic effectsPlacebo-controlled phase 1 clinical trialBiomarkers of AD pathologyClinical trialsCognitive measuresNominally significant differencesPhase 1 clinical trialModel of ADHippocampal cortexPhase 1/2 studyRating ScaleParallel-group trialSynaptic densityTrial registrationThe clinical trialPlacebo-controlledSigma-2 receptor ligands
2023
Tau epicenter identification and connectivity in clinically heterogeneous Alzheimer’s disease variants
Trainer A, Xu W, Chase A, O'Dell R, Tun S, Li J, Ju S, van Dyck C, Mecca A, Fredricks C. Tau epicenter identification and connectivity in clinically heterogeneous Alzheimer’s disease variants. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079435.Peer-Reviewed Original ResearchAmnestic Alzheimer's diseaseLogopenic variant primary progressive aphasiaPosterior cortical atrophyFunctional connectivity mapsHigher tau burdenFunctional connectivityTau burdenAlzheimer's diseaseConnectivity mapsLongitudinal tau-PETSpread of tauVariant primary progressive aphasiaFusiform gyrusFrontal eye fieldPrimary progressive aphasiaBrains of participantsTau PET scansSuperior parietal lobulePatient-specific biomarkersCortical atrophyCommon subtypeTau-PETHealthy controlsParietooccipital cortexPET scansAssessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET
Silva-Rudberg J, Salardini E, O'Dell R, Chen M, Ra J, Georgelos J, Morehouse M, Melino K, Varma P, Toyonaga T, Nabulsi N, Huang Y, Carson R, van Dyck C, Mecca A. Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET. American Journal Of Geriatric Psychiatry 2023, 32: 17-28. PMID: 37673749, PMCID: PMC10840732, DOI: 10.1016/j.jagp.2023.08.002.Peer-Reviewed Original ResearchSynaptic densityAlzheimer's diseaseMean diffusivitySynaptic lossGray matter microstructureGray matter mean diffusivityDisease pathologyHippocampal synaptic densityMajor pathological correlateSetting of ADAD-related neuropathologySynaptic vesicle glycoprotein 2AHippocampal mean diffusivityAlzheimer's disease pathologyAmyloid-positive participantsMatter mean diffusivityPositron emission tomography (PET) imagingEmission Tomography ImagingGray matter structuresPathological correlatesPositive participantsInverse associationAD groupCognitive impairmentDiseasePrincipal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
O'Dell R, Higgins-Chen A, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Ni G, Chupak A, Zhao W, Salardini E, Nabulsi N, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease. NeuroImage Clinical 2023, 39: 103457. PMID: 37422964, PMCID: PMC10338149, DOI: 10.1016/j.nicl.2023.103457.Peer-Reviewed Original ResearchConceptsCognitive domainsCognitive performanceSubjects' scoresCortical regionsNeuropsychological batteryEarly Alzheimer's diseaseAD groupBilateral regionsNormal participantsNegative loadingsCognitive impairmentCN participantsAlzheimer's diseaseParticipantsStructural correlatesStrong contributionParticipant characteristicsScoresPositive loadingsData-driven approachTotal variancePrincipal component analysisSpecific spatial patternsDisease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials
Van Dyck C, O'Dell R, Mecca A. Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12388. PMID: 37187779, PMCID: PMC10175943, DOI: 10.1002/trc2.12388.Peer-Reviewed Original Research
2021
Generation of synthetic PET images of synaptic density and amyloid from 18F‐FDG images using deep learning
Wang R, Liu H, Toyonaga T, Shi L, Wu J, Onofrey JA, Tsai Y, Naganawa M, Ma T, Liu Y, Chen M, Mecca AP, O’Dell R, van Dyck C, Carson RE, Liu C. Generation of synthetic PET images of synaptic density and amyloid from 18F‐FDG images using deep learning. Medical Physics 2021, 48: 5115-5129. PMID: 34224153, PMCID: PMC8455448, DOI: 10.1002/mp.15073.Peer-Reviewed Original ResearchAmyloid-Associated Depression—or Not?
van Dyck CH, O'Dell RS, Mecca AP. Amyloid-Associated Depression—or Not? Biological Psychiatry 2021, 89: 737-738. PMID: 33766236, PMCID: PMC8396710, DOI: 10.1016/j.biopsych.2021.02.008.Peer-Reviewed Original ResearchComparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study
Chen MK, Mecca AP, Naganawa M, Gallezot JD, Toyonaga T, Mondal J, Finnema SJ, Lin SF, O’Dell R, McDonald JW, Michalak HR, Vander Wyk B, Nabulsi NB, Huang Y, Arnsten AF, van Dyck CH, Carson RE. Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study. Cerebrovascular And Brain Metabolism Reviews 2021, 41: 2395-2409. PMID: 33757318, PMCID: PMC8393289, DOI: 10.1177/0271678x211004312.Peer-Reviewed Original ResearchConceptsSynaptic densityMedial temporal regionsAlzheimer's diseaseNeocortical regionsTemporal regionsRelative outcome measuresMedial temporal lobeVivo PET imagingJ bindingOutcome measuresTemporal lobeMagnitude of reductionCN participantsBrain regionsAD participantsDiseasePET imagingConcordant reductionNormal participantsSynaptic vesiclesPerfusionMetabolismSuitable markerParticipantsSimilar patternAssociation 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 correlates
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