2023
Mass spectrometry on cerebrospinal fluid uncovers association of novel glycolysis biomarkers with Alzheimer’s disease in a complex clinical cohort
de Geus M, Leslie S, Wang W, Lam T, Broekman M, Neefjes S, Nairn A, Carlyle B, Arnold S. Mass spectrometry on cerebrospinal fluid uncovers association of novel glycolysis biomarkers with Alzheimer’s disease in a complex clinical cohort. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.078466.Peer-Reviewed Original ResearchAlzheimer's diseaseMild cognitive impairmentHospital neurology serviceNon-AD diagnosesDiagnostic lumbar puncturePrognosis of ADCerebrospinal fluid biomarkersClinic cohortFurther mechanistic studiesNeurology serviceFDG-PETBrain metabolismFluid biomarkersLumbar puncturePatient cohortClinical indicationsDisease progressionATN biomarkersClinical cohortTreatment responseComplex cohortBackground DiagnosisCSF samplesTreatment efficacyLinear regression analysisChronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques
Bathla S, Datta D, Liang F, Barthelemy N, Wiseman R, Slusher B, Asher J, Zeiss C, Ekanayake‐Alper D, Holden D, Terwilliger G, Duque A, Arellano J, van Dyck C, Bateman R, Xie Z, Nairn A, Arnsten A. Chronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12431. PMID: 37915375, PMCID: PMC10617575, DOI: 10.1002/trc2.12431.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseEntorhinal cortexGCPII inhibitionDorsolateral prefrontal cortexChronic inhibitionTau pathologyTau hyperphosphorylationAged macaquesType 3 metabotropic glutamate receptorAlzheimer's diseasePrefrontal cortexRhesus macaquesVehicle-treated monkeysAged rhesus macaquesMetabotropic glutamate receptorsApparent side effectsAmyloid beta 1Regulation of calciumGCPII inhibitorsKey etiological factorGCPII activityPrimate dlPFCNeuronal damageCSF analysisCalcium dysregulation
2022
Applying Data‐Independent Acquisition Mass Spectrometry on Cerebrospinal Fluid Samples from a Neurology Clinic for Biomarker Discovery in Alzheimer’s Disease
de Geus M, Leslie S, Ramirez C, Trombetta B, Wang W, Lam T, Gotti C, Roux‐Dalvai F, Droit A, Nairn A, Arnold S, Carlyle B. Applying Data‐Independent Acquisition Mass Spectrometry on Cerebrospinal Fluid Samples from a Neurology Clinic for Biomarker Discovery in Alzheimer’s Disease. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.064314.Peer-Reviewed Original ResearchAlzheimer's diseaseMild cognitive impairmentPatient cohortAD-specific biomarkersNon-AD diagnosesPrognosis of ADCerebrospinal fluid samplesNeurology clinicBrain metabolismFluid biomarkersAD progressionCognitive prognosisComplex cohortBackground DiagnosisTreatment efficacyDementia diagnosisLarge-scale patient cohortsPathophysiological processesSpecific biomarkersRegulation of balanceDiagnosisCognitive AssessmentDiseaseCohortBiomarkersDiagnostic and Prognostic Performance of the Modified Lumipulse pTau 181 Assay in Plasma for Alzheimer’s Disease
Wilson E, Young C, Benitez J, Vandijck M, Swarovski M, Shahid M, Corso N, Kennedy G, Trelle A, Channappa D, Belnap M, Lind B, Le Bastard N, Quinn J, Nairn A, Kerchner G, Sha S, Wagner A, Henderson V, Longo F, Wyss‐Coray T, Poston K, Mormino E, Andreasson K. Diagnostic and Prognostic Performance of the Modified Lumipulse pTau 181 Assay in Plasma for Alzheimer’s Disease. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.060879.Peer-Reviewed Original ResearchAlzheimer's Disease Research CenterPtau-181Disease Research CenterAlzheimer's diseaseCohort 1Positron emission tomographyCohort 2Prognostic performanceAntibody combinationsAD participantsAβ42/Aβ40 ratioPreclinical Alzheimer's diseaseClinical AD diagnosisPlasma p-tau181Longitudinal cognitive declineTau pathologyAD pathologyCSF biomarkersTau-PETP-tau181Outcome measuresPhosphorylated tauPET biomarkersAβ40 ratioCognitive declinePerformance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease
Wilson E, Young C, Ramos Benitez J, Swarovski M, Feinstein I, Vandijck M, Le Guen Y, Kasireddy N, Shahid M, Corso N, Wang Q, Kennedy G, Trelle A, Lind B, Channappa D, Belnap M, Ramirez V, Skylar-Scott I, Younes K, Yutsis M, Le Bastard N, Quinn J, van Dyck C, Nairn A, Fredericks C, Tian L, Kerchner G, Montine T, Sha S, Davidzon G, Henderson V, Longo F, Greicius M, Wagner A, Wyss-Coray T, Poston K, Mormino E, Andreasson K. Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease. Alzheimer's Research & Therapy 2022, 14: 172. PMID: 36371232, PMCID: PMC9652927, DOI: 10.1186/s13195-022-01116-2.Peer-Reviewed Original ResearchConceptsPlasma p-tau181Alzheimer's Disease Research CenterP-tau181Disease Research CenterAlzheimer's diseasePositron emission tomographyAD dementiaBlood-based biomarker assaysAmyloid positron emission tomographyTreatment monitoringNovel blood-based biomarkersCSF p-tau181P-tau181 concentrationsDisease-modifying therapiesAβ42/Aβ40 ratioBlood-based biomarkersClinical AD diagnosisDetection of ADMild cognitive impairmentStudy cohortCSF biomarkersPlasma levelsAD groupPrognostic performanceCDR sum
2020
Identification of NPTX2 as a prognostic biomarker of Alzheimer’s disease through a longitudinal CSF proteomics study in ADNI subjects
Libiger O, Shaw L, Watson M, Nairn A, Umaña K, Canet‐Avilés R, Jack C, Breton Y, Cortes L, Chelsky D, Spellman D, Baker S, Raghavan N, Potter W. Identification of NPTX2 as a prognostic biomarker of Alzheimer’s disease through a longitudinal CSF proteomics study in ADNI subjects. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.047605.Peer-Reviewed Original ResearchP-Tau 181Alzheimer's diseasePrognostic biomarkerRate of declineADNI subjectsLongitudinal changesTau-tangle pathologyBaseline clinical diagnosisAssociation of changesPre-specified analysis planMild cognitive impairmentTangle pathologyClinical progressionMixed-effects linear modelNegative subjectsClinical prognosisDisease continuumAdditional biomarkersAmyloid plaquesDrug development effortsNormal subjectsSubset of individualsRetrospective investigationBiomarker profilesPathologic processesBiochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex
Leslie S, Datta D, Wang M, van Dyck C, Arnsten A, Nairn A. Biochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.042017.Peer-Reviewed Original ResearchTau pathologyAge-related dysregulationAlzheimer's diseaseIntracellular calciumTau phosphorylationRhesus monkeysRat primary cortical culturesHuman post-mortem samplesVulnerable brain regionsSporadic Alzheimer's diseaseAmyloid-beta plaquesPrimary cortical culturesMain pathological hallmarksRhesus monkey cortexTau neurofibrillary tanglesYears of ageEarly-onset formAge-related vulnerabilityDorsolateral prefrontal cortexAge-related changesMonkey DLPFCPost-mortem samplesAD pathologyAmyloid pathologyUnknown etiology
2001
Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer’s disease
Kim S, Nairn A, Cairns N, Lubec G. Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer’s disease. Journal Of Neural Transmission. Supplementa 2001, 263-272. PMID: 11771749, DOI: 10.1007/978-3-7091-6262-0_21.Peer-Reviewed Original ResearchConceptsARPP-19Protein kinaseDifferential display polymerase chain reactionAlzheimer's diseaseDown syndromeCAMP-dependent protein kinaseTemporal cortexActivity of PKASignal transductionDownregulated sequenceBrain regionsNeurodegenerative disordersDiseaseImpaired mechanismsProtein levelsDecreased activityChain reactionFirst evidenceSignificant reductionSyndromeCortexDisordersTransductionHomologyKinase
1999
Phosphorylation of the Cytoplasmic Domain of Alzheimer's β-Amyloid Precursor Protein at Ser655 by a Novel Protein Kinase
Isohara T, Horiuchi A, Watanabe T, Ando K, Czernik A, Uno I, Greengard P, Nairn A, Suzuki T. Phosphorylation of the Cytoplasmic Domain of Alzheimer's β-Amyloid Precursor Protein at Ser655 by a Novel Protein Kinase. Biochemical And Biophysical Research Communications 1999, 258: 300-305. PMID: 10329382, DOI: 10.1006/bbrc.1999.0637.Peer-Reviewed Original ResearchConceptsNovel protein kinaseAlzheimer's beta-amyloid precursor proteinProtein kinase CExtracellular signal-regulated kinaseProtein kinaseCytoplasmic domainCalmodulin-dependent protein kinase IIΒ-amyloid precursor proteinPrecursor proteinAlzheimer's β-Amyloid Precursor ProteinSignal-regulated kinaseProtein kinase IIBeta-amyloid precursor proteinKinase IUnidentified proteinsKinase IIKinase CKinaseSer655ProteinAlzheimer's diseaseThr654Rat brainPhosphorylationDomain
1993
Protein Phosphorylation Regulates the Cellular Trafficking and Processing of the Alzheimer Beta/A4 Amyloid Precursor Protein
Caporaso G, Gandy S, Buxbaum J, Suzuki T, Nordstedt C, Iverfeldt K, Ramabhadran T, Czernik A, Nairn A, Greengard P. Protein Phosphorylation Regulates the Cellular Trafficking and Processing of the Alzheimer Beta/A4 Amyloid Precursor Protein. NATO ASI Series 1993, 201-202. DOI: 10.1007/978-3-662-02928-2_42.Peer-Reviewed Original ResearchAmyloid precursor proteinBeta/A4 amyloid peptideAlzheimer's diseaseBeta/A4 amyloid precursor proteinA4 amyloid precursor proteinAlzheimer beta/A4 amyloid precursor proteinBeta/A4 peptideA4 amyloid peptidePrecursor proteinEarly-onset formAPP metabolismCerebral depositionA4 peptidePC12 cell lineAbnormal processingNeuroendocrine PC12 cell lineDiseaseCellular traffickingCell linesAmyloid peptidesNormal cellular traffickingTransmembrane glycoproteinProteolytic processingProtein phosphorylationPhosphorylation
1992
Increased phosphorylation of elongation factor 2 in Alzheimer's disease
Johnson G, Gotlib J, Haroutunian V, Bierer L, Nairn A, Merril C, Wallace W. Increased phosphorylation of elongation factor 2 in Alzheimer's disease. Brain Research 1992, 15: 319-326. PMID: 1331687, DOI: 10.1016/0169-328x(92)90124-t.Peer-Reviewed Original ResearchConceptsDisease brainAlzheimer's diseaseAlzheimer's disease brainFactor 2AD homogenatesAD tissueElongation factor 2Brain homogenatesSame brainDiseaseVariant isoformsProtein synthesisPhosphorylated formInhibits protein synthesisBrainUnaffected areasHomogenatesAcidic isoformsPhosphorylationGene expressionEF-2Protein Phosphorylation Regulates Processing of the Alzheimer β/A4-Amyloid Precursor Protein
Gandy S, Caporaso G, Ramabhadran T, Buxbaum J, Suzuki T, Nordstedt C, Iverfeldt K, Czernik A, Nairn A, Greengard P. Protein Phosphorylation Regulates Processing of the Alzheimer β/A4-Amyloid Precursor Protein. Research And Perspectives In Alzheimer's Disease 1992, 130-143. DOI: 10.1007/978-3-642-46776-9_14.Peer-Reviewed Original Research