2024
Glutamatergic Dysfunction in Autism Spectrum Disorder (P1-8.001)
Brasic J, Nandi A, Russell D, Jennings D, Barret O, Slifer K, Sedlak T, Seibyl J, Berry-Kravis E, Wong D, Budimirovic D. Glutamatergic Dysfunction in Autism Spectrum Disorder (P1-8.001). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000204347.Peer-Reviewed Original Research
2023
Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration
Koga S, Metrick M, Golbe L, Santambrogio A, Kim M, Soto-Beasley A, Walton R, Baker M, De Castro C, DeTure M, Russell D, Navia B, Sandiego C, Ross O, Vendruscolo M, Caughey B, Dickson D. Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration. Acta Neuropathologica Communications 2023, 11: 88. PMID: 37264457, PMCID: PMC10236843, DOI: 10.1186/s40478-023-01584-z.Peer-Reviewed Original ResearchConceptsSuperior frontal gyrusFrontal gyrusConsistent with corticobasal degenerationConsistent with progressive supranuclear palsyMotor cortexCorticobasal degenerationProgressive supranuclear palsyPosterior cortical areasPresentation of corticobasal degenerationSubtype of frontotemporal lobar degenerationRichardson's syndromeBrain regionsOccipital cortexSubcortical structuresCaudate nucleusFrontotemporal lobar degenerationTau PET scansSubstantia nigraGlobus pallidusCorticobasal syndromeGyrusSupranuclear palsyCortexCortical areasClinical presentation of progressive supranuclear palsy
2022
In Vivo Head‐To‐Head Comparison of [18F]GTP1 and [18F]PI2620 in Alzheimer’s Disease
Bohorquez S, Constantinescu C, Manser P, Gunn R, Russell D, Tonietto M, Bullich S, Stephens A, Mueller A, Klein G, Teng E, Pickthorn K. In Vivo Head‐To‐Head Comparison of [18F]GTP1 and [18F]PI2620 in Alzheimer’s Disease. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.063517.Peer-Reviewed Original ResearchChoroid plexusAlzheimer's diseaseTau pathology distributionModerate AD subjectsTarget cortical regionsTherapeutic trialsTau pathologyHead studiesPathology distributionCentrum semiovaleCortical greyBraak regionsAD subjectsHuman studiesInferior cerebellumSubcortical regionsHead comparisonQuantification scaleCortical regionsSubcortical structuresMinute imagesCSF spaceDiseaseUnimpaired subjectsSUVRPROGRESS IN DEVELOPING A LIGHT‐STABLE 4R TAU PET IMAGING AGENT: APN‐1701 FIH
Tempest P, Lin Y, Tai C, Ono M, Russell D, Sandiego C, Carroll V, Gunn R, Margolin R, Higuchi M, Jang M. PROGRESS IN DEVELOPING A LIGHT‐STABLE 4R TAU PET IMAGING AGENT: APN‐1701 FIH. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.063028.Peer-Reviewed Original ResearchAD subjectsMulticenter phase 2 clinical trialAlzheimer's diseasePhase 2 clinical trialTau PET tracersPET imaging agentSimilar brain regionsCortical uptakeTest-retest studyCN subjectsClinical trialsNormal subjectsTau tracersBrain regionsSUV valuesDiverse tauopathiesPET tracersSame rank orderSUVR imagesImaging agentImaging profileDiseaseIn Vivo Head‐To‐Head Comparison of [18F]GTP1 and [18F]PI2620 in Alzheimer’s Disease
Bohorquez S, Constantinescu C, Manser P, Gunn R, Russell D, Tonietto M, Bullich S, Stephens A, Mueller A, Klein G, Teng E, Pickthorn K. In Vivo Head‐To‐Head Comparison of [18F]GTP1 and [18F]PI2620 in Alzheimer’s Disease. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.063513.Peer-Reviewed Original ResearchChoroid plexusAlzheimer's diseaseTau pathology distributionModerate AD subjectsTarget cortical regionsTherapeutic trialsTau pathologyHead studiesPathology distributionCentrum semiovaleCortical greyBraak regionsAD subjectsHuman studiesInferior cerebellumSubcortical regionsHead comparisonQuantification scaleCortical regionsSubcortical structuresMinute imagesCSF spaceDiseaseUnimpaired subjectsSUVRPROGRESS IN DEVELOPING A LIGHT‐STABLE 4R TAU PET IMAGING AGENT: APN‐1701 FIH
Tempest P, Lin Y, Tai C, Ono M, Russell D, Sandiego C, Gunn R, Carroll V, Margolin R, Kao T, Higuchi M, Jang M. PROGRESS IN DEVELOPING A LIGHT‐STABLE 4R TAU PET IMAGING AGENT: APN‐1701 FIH. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.063025.Peer-Reviewed Original ResearchAD subjectsMulticenter phase 2 clinical trialAlzheimer's diseasePhase 2 clinical trialTau PET tracersPET imaging agentSimilar brain regionsCortical uptakeTest-retest studyCN subjectsClinical trialsNormal subjectsTau tracersBrain regionsSUV valuesDiverse tauopathiesPET tracersSame rank orderSUVR imagesImaging agentImaging profileDisease
2021
Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme, following administration of single and multiple doses to healthy volunteers
Kielbasa W, Shcherbinin S, Goldsmith P, Phipps K, Biglan K, Mancini M, Russell D, Constantinescu C, Gunn R, Nuthall H, Mergott D, Lowe S, Collins E. Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme, following administration of single and multiple doses to healthy volunteers. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.057774.Peer-Reviewed Original ResearchHealthy volunteersEnzyme occupancyPET scansSingle doseMultiple-dose clinical studiesPost-dose intervalPositron emission tomography radioligandBaseline PET scanLonger clinical trialsTarget occupancyTau-related diseasesMultiple dosesMultiple dosingClinical trialsPlasma pharmacokineticsClinical studiesEfficacy trialsSD studiesDose selectionTomography radioligandEnzyme inhibitorsPotential treatmentAlzheimer's diseasePET studiesTarget engagementMEASUREMENT OF CEREBRAL EXPRESSION OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 5 IN AUTISM SPECTRUM DISORDER AND FRAGILE X SYNDROME
Brasic J, Budimirovic D, Nandi A, Russell D, Jennings D, Barret O, Martin S, Sllifer K, Berry-Kravis E, Wong D. MEASUREMENT OF CEREBRAL EXPRESSION OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 5 IN AUTISM SPECTRUM DISORDER AND FRAGILE X SYNDROME. Journal Of The American Academy Of Child & Adolescent Psychiatry 2021, 60: s257. DOI: 10.1016/j.jaac.2021.09.413.Peer-Reviewed Original ResearchReduced Metabotropic Glutamate Receptor Subtype 5 in Fragile X Syndrome (4378)
Brasic J, Nandi A, Russell D, Jennings D, Barret O, Mathur A, Slifer K, Sedlak T, Martin S, Brinson Z, Vyas P, Seibyl J, Berry-Kravis E, Wong D, Budimirovic D. Reduced Metabotropic Glutamate Receptor Subtype 5 in Fragile X Syndrome (4378). Neurology 2021, 96 DOI: 10.1212/wnl.96.15_supplement.4378.Peer-Reviewed Original Research
2020
Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme: Translation from rat to human
Shcherbinin S, Kielbasa W, Dubois S, Lowe S, Phipps K, Tseng J, Kevin D, Natanegara F, Warner S, Dreyfus N, Lindsay‐Scott P, Hawk M, McDonald N, Zhang X, Gilmore J, Biglan K, Mergott D, Russell D, Gunn R, Constantinescu C, Nuthall H, Collins E. Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme: Translation from rat to human. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.040558.Peer-Reviewed Original ResearchPET scansEnzyme occupancyHealthy volunteersPlasma concentration-dependent increaseSingle oral dose studyOral dose studyBaseline PET scanSingle oral doseTau-related diseasesDose-dependent changesConcentration-dependent increaseHuman PET studiesDose cohortsOral doseSingle dosesDose studyClinical studiesEfficacy trialsPharmacokinetic samplesFrontal cortexInitial cohortDose selectionHigh doseNumber of subjectsEnzyme inhibitorsPerfusion-Phase 18 F-PI-2620 Tau-PET Imaging as a Surrogate Marker of Neuronal Injury
Beyer L, Nitschmann A, Barthel H, van Eimeren T, Unterrainer M, Sauerbeck J, Song M, Schroeter M, Russell D, Stephens A, Herms J, Levin J, Classen J, Höglinger G, Bartenstein P, Villemagne V, Drzezga A, Seibyl J, Sabri O, Brendel M. Perfusion-Phase 18 F-PI-2620 Tau-PET Imaging as a Surrogate Marker of Neuronal Injury. Nuklearmedizin - NuclearMedicine 2020, 59: 166. DOI: 10.1055/s-0040-1708352.Peer-Reviewed Original ResearchBinding characteristics of 18 F-PI-2620 differentiate the clinically predicted tau isoform in suspected 3/4-repeat and 4-repeat tauopathies
Song M, Barthel H, van Eimeren T, Marek K, Beyer L, Sauerbeck J, Barbe M, Schroeter M, Russell D, Stephens A, Herms J, Levin J, Classen J, Höglinger G, Bartenstein P, Villemagne V, Drzezga A, Seibyl J, Sabri O, Brendel M. Binding characteristics of 18 F-PI-2620 differentiate the clinically predicted tau isoform in suspected 3/4-repeat and 4-repeat tauopathies. Nuklearmedizin - NuclearMedicine 2020, 59: 106. DOI: 10.1055/s-0040-1708171.Peer-Reviewed Original Research18 F-PI2620 Tau-PET in Progressive Supranuclear Palsy – A Multi-Center Evaluation
Brendel M, Barthel H, van Eimeren T, Marek K, Beyer L, Song M, Sauerbeck J, Barbe M, Schroeter M, Russell D, Stephens A, Herms J, Levin J, Classen J, Höglinger G, Bartenstein P, Villemagne V, Drzezga A, Seibyl J, Sabri O. 18 F-PI2620 Tau-PET in Progressive Supranuclear Palsy – A Multi-Center Evaluation. Nuklearmedizin - NuclearMedicine 2020, 59: 89. DOI: 10.1055/s-0040-1708120.Peer-Reviewed Original Research
2018
Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4)
Beach T, Serrano G, Kremer T, Canamero M, Dziadek S, Sade H, Derkinderen P, Corbillé A, Letournel F, Munoz D, White C, Schneider J, Crary J, Sue L, Adler C, Glass M, Intorcia A, Walker J, Foroud T, Coffey C, Ecklund D, Riss H, Goßmann J, König F, Kopil C, Arnedo V, Riley L, Linder C, Dave K, Jennings D, Seibyl J, Mollenhauer B, Chahine L, Guilmette L, Russell D, Noyes-Lloyd C, Mitchell C, Smith D, Potter M, Case R, Lott D, Duffy A, Hogarth P, Cresswell M, Akhtar R, Purri R, Amara A, Blair C, Keshavarzian A, Marras C, Visanji N, Rothberg B, Oza V. Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4). Journal Of Neuropathology & Experimental Neurology 2018, 77: 793-802. PMID: 30107604, PMCID: PMC6097838, DOI: 10.1093/jnen/nly056.Peer-Reviewed Original ResearchConceptsParkinson's diseaseASyn pathologyΑ-synuclein pathologySubmandibular gland biopsyPeripheral biopsiesControl subjectsGland biopsyBlinded panelImmunohistochemical methodsImmunoperoxidase methodMonoclonal antibodiesScore agreementNeuropathologistsPathologyBiopsySkinSubsequent testingSampling studyT156. IN VIVO CHARACTERIZATION OF THE FIRST AGONIST DOPAMINE D1 RECEPTORS PET IMAGING TRACER [18F]MNI-968 IN HUMAN
Tamagnan G, Barret O, Alagille D, Carroll V, Madonia J, Constantinescu C, SanDiego C, Papin C, Morley T, Russell D, McCarthy T, Zhang L, Gray D, Villalobos A, Lee C, Chen J, Seibyl J, Marek K. T156. IN VIVO CHARACTERIZATION OF THE FIRST AGONIST DOPAMINE D1 RECEPTORS PET IMAGING TRACER [18F]MNI-968 IN HUMAN. Schizophrenia Bulletin 2018, 44: s176-s176. PMCID: PMC5888516, DOI: 10.1093/schbul/sby016.432.Peer-Reviewed Original ResearchLogan graphical analysisNon-human primatesRhesus monkeysD1 receptorsBlockade studiesPET studiesPET radiotracersD1 receptor occupancyWhole-brain uptakeNovel PET radiotracersInhibitory G proteinSame dose levelMin post injectionHealthy human volunteersTest-retest reproducibilityBrain PET studiesPET imaging tracerAgonist PET tracerClinical studiesStriatal regionsInjected dosePsychiatric disordersCerebellar cortexDose levelsReceptor occupancy
2015
O4‐07‐06: Approaches to quantitative analysis of the PET tau radiotracer [18F]AV1451
Seibyl J, Barret O, Alagille D, Jennings D, Russell D, Marek K, Tamagnan G. O4‐07‐06: Approaches to quantitative analysis of the PET tau radiotracer [18F]AV1451. Alzheimer's & Dementia 2015, 11: p285-p285. DOI: 10.1016/j.jalz.2015.07.386.Peer-Reviewed Original ResearchMonitoring loss of striatal phosphodiesterase 10A (PDE10A) with [ 18 F]MNI-659 and PET: A biomarker of early Huntington disease (HD) progression. (I11-4A)
Russell D, Jennings D, Barret O, Tamagnan G, Carroll V, Alagille D, Morley T, Papin C, Seibyl J, Marek K. Monitoring loss of striatal phosphodiesterase 10A (PDE10A) with [ 18 F]MNI-659 and PET: A biomarker of early Huntington disease (HD) progression. (I11-4A). Neurology 2015, 84 DOI: 10.1212/wnl.84.14_supplement.i11-4a.Peer-Reviewed Original ResearchMonitoring loss of striatal phosphodiesterase 10A (PDE10A) with [ 18 F]MNI-659 and PET: A biomarker of early Huntington disease (HD) progression. (S15.004)
Russell D, Jennings D, Barret O, Tamagnan G, Carroll V, Alagille D, Morley T, Papin C, Seibyl J, Marek K. Monitoring loss of striatal phosphodiesterase 10A (PDE10A) with [ 18 F]MNI-659 and PET: A biomarker of early Huntington disease (HD) progression. (S15.004). Neurology 2015, 84 DOI: 10.1212/wnl.84.14_supplement.s15.004.Peer-Reviewed Original Research
2014
A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease: No Evidence of Benefit
Beal M, Oakes D, Shoulson I, Henchcliffe C, Galpern W, Haas R, Juncos J, Nutt J, Voss T, Ravina B, Shults C, Helles K, Snively V, Lew M, Griebner B, Watts A, Gao S, Pourcher E, Bond L, Kompoliti K, Agarwal P, Sia C, Jog M, Cole L, Sultana M, Kurlan R, Richard I, Deeley C, Waters C, Figueroa A, Arkun A, Brodsky M, Ondo W, Hunter C, Jimenez-Shahed J, Palao A, Miyasaki J, So J, Tetrud J, Reys L, Smith K, Singer C, Blenke A, Russell D, Cotto C, Friedman J, Lannon M, Zhang L, Drasby E, Kumar R, Subramanian T, Ford D, Grimes D, Cote D, Conway J, Siderowf A, Evatt M, Sommerfeld B, Lieberman A, Okun M, Rodriguez R, Merritt S, Swartz C, Martin W, King P, Stover N, Guthrie S, Watts R, Ahmed A, Fernandez H, Winters A, Mari Z, Dawson T, Dunlop B, Feigin A, Shannon B, Nirenberg M, Ogg M, Ellias S, Thomas C, Frei K, Bodis-Wollner I, Glazman S, Mayer T, Hauser R, Pahwa R, Langhammer A, Ranawaya R, Derwent L, Sethi K, Farrow B, Prakash R, Litvan I, Robinson A, Sahay A, Gartner M, Hinson V, Markind S, Pelikan M, Perlmutter J, Hartlein J, Molho E, Evans S, Adler C, Duffy A, Lind M, Elmer L, Davis K, Spears J, Wilson S, Leehey M, Hermanowicz N, Niswonger S, Shill H, Obradov S, Rajput A, Cowper M, Lessig S, Song D, Fontaine D, Zadikoff C, Williams K, Blindauer K, Bergholte J, Propsom C, Stacy M, Field J, Mihaila D, Chilton M, Uc E, Sieren J, Simon D, Kraics L, Silver A, Boyd J, Hamill R, Ingvoldstad C, Young J, Thomas K, Kostyk S, Wojcieszek J, Pfeiffer R, Panisset M, Beland M, Reich S, Cines M, Zappala N, Rivest J, Zweig R, Lumina L, Hilliard C, Grill S, Kellermann M, Tuite P, Rolandelli S, Kang U, Young J, Rao J, Cook M, Severt L, Boyar K. A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease: No Evidence of Benefit. JAMA Neurology 2014, 71: 543-552. PMID: 24664227, DOI: 10.1001/jamaneurol.2014.131.Peer-Reviewed Original ResearchConceptsTotal UPDRS scoresUPDRS scoresCoenzyme Q10PD medicationsFinal visitClinical benefitClinical trialsEarly-phase human studiesPrevious phase II studyDouble-blind clinical trialMini-Mental State Examination scoreParticipants 30 yearsPhase III randomizedPrespecified futility criterionDrug-induced parkinsonismPhase II studyActive treatment groupIU/dEarly Parkinson's diseaseHistory of strokePossible clinical benefitPrimary outcome measureState Examination scoreParkinson's disease modelDiagnosis of PD
2013
Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease
Kang J, Irwin D, Chen-Plotkin A, Siderowf A, Caspell C, Coffey C, Waligórska T, Taylor P, Pan S, Frasier M, Marek K, Kieburtz K, Jennings D, Simuni T, Tanner C, Singleton A, Toga A, Chowdhury S, Mollenhauer B, Trojanowski J, Shaw L, Lasch S, Flagg E, Poewe W, Sherer T, Meunier C, Rudolph A, Casaceli C, Seibyl J, Mendick S, Schuff N, Uribe L, Yankey J, Crawford K, Scutti A, Casalin P, Malferrari G, Hawkins K, Russell D, Leary L, Factor S, Sommerfeld B, Hogarth P, Pighetti E, Williams K, Standaert D, Guthrie S, Hauser R, Jankovic J, Hunter C, Stern M, Darin A, Leverenz J, Baca M, Frank S, Thomas C, Richard I, Deeley C, Rees L, Sprenger F, Oertel W, Willeke D, Shill H, Fernandez H, Mule J, Berg D, Gauss K, Galasko D, Fontaine D, Mari Z, McCoy A, Brooks D, Shah B, Barone P, Isaacson S, James A, Espay A, Espay K, Rowe D, Ranola M. Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease. JAMA Neurology 2013, 70: 1277-1287. PMID: 23979011, PMCID: PMC4034348, DOI: 10.1001/jamaneurol.2013.3861.Peer-Reviewed Original ResearchConceptsDrug-naive patientsEarly Parkinson's diseaseCSF biomarkersΒ-amyloid 1CSF Aβ1-42P-tau181Parkinson's diseaseT-tauAβ1-42Healthy controlsΑ-synucleinClinical featuresPPMI cohortParkinson's Progression Markers Initiative (PPMI) studyLower CSF Aβ1-42Early-stage Parkinson's diseaseT-tau/Aβ1Lower Aβ1-42P-tau181 concentrationsCSF t-tauΑ-synuclein levelsCerebrospinal fluid levelsCross-sectional studyEnzyme-linked immunosorbent assaySignificant correlation