2024
A 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
Assessment 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 impairmentDisease
2021
Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease
Mecca AP, Chen MK, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Banks ER, Ni GS, Rogers K, Gallezot JD, Ropchan J, Emery PR, Nabulsi NB, Vander Wyk BC, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease. Neurobiology Of Aging 2021, 111: 44-53. PMID: 34963063, PMCID: PMC8761170, DOI: 10.1016/j.neurobiolaging.2021.11.004.Peer-Reviewed Original ResearchConceptsHippocampal synaptic densitySynaptic densityAlzheimer's diseaseCortical tau depositionEarly neuropathologic changesInitial clinical featuresSynaptic vesicle glycoprotein 2AEarly Alzheimer's diseaseOverall sampleEntorhinal cortical cellsClinical featuresNeuropathologic changesTau depositionTau pathologyInverse associationPerforant pathAD groupSynaptic failureNormal cognitionOlder individualsEarly degenerationDiseaseNormal participantsHippocampusTau
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