0000000000920101

AUTHOR

Jeffrey Kaye

showing 2 related works from this author

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

2017

International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…

0301 basic medicineLinkage disequilibrium[SDV]Life Sciences [q-bio]MedizinSequence HomologyGenome-wide association studygenetics [Alzheimer Disease]metabolism [Microglia]Linkage Disequilibrium0302 clinical medicinegenetics [Protein Interaction Maps]genetics [Membrane Glycoproteins]Gene FrequencyImmunologicgenetics [Adaptor Proteins Signal Transducing]Receptorsgenetics [Exome]Odds RatioInnategenetics [Receptors Immunologic]ExomeProtein Interaction Mapsgenetics [Genetic Predisposition to Disease]Receptors ImmunologicABI3 protein humanGeneticsAdaptor Proteins Signal Transducing; Alzheimer Disease; Amino Acid Sequence; Case-Control Studies; Exome; Gene Expression Profiling; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Immunity Innate; Linkage Disequilibrium; Membrane Glycoproteins; Microglia; Odds Ratio; Phospholipase C gamma; Protein Interaction Maps; Receptors Immunologic; Sequence Homology Amino Acid; Polymorphism Single Nucleotide; GeneticsMembrane GlycoproteinsAdaptor ProteinsSingle NucleotideAdaptor Proteins Signal Transducing; Alzheimer Disease; Amino Acid Sequence; Case-Control Studies; Exome; Gene Expression Profiling; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Immunity Innate; Linkage Disequilibrium; Membrane Glycoproteins; Microglia; Odds Ratio; Phospholipase C gamma; Protein Interaction Maps; Receptors Immunologic; Sequence Homology Amino Acid; Polymorphism Single Nucleotide3. Good health[SDV] Life Sciences [q-bio]Amino AcidSettore MED/26 - NEUROLOGIAgenetics [Phospholipase C gamma][SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]MicrogliaAlzheimer's diseaseCommon disease-common variantGenotypeBiologyPolymorphism Single NucleotideArticle03 medical and health sciencesAlzheimer Diseaseddc:570medicineJournal ArticleGeneticsHumansGenetic Predisposition to Disease[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Amino Acid SequencePolymorphismAllele frequencyAdaptor Proteins Signal TransducingTREM2 protein humanSequence Homology Amino AcidTREM2Phospholipase C gammaGene Expression ProfilingCase-control studySignal TransducingImmunitymedicine.diseaseR1Immunity InnateMinor allele frequencygenetics [Immunity Innate]030104 developmental biologyCase-Control StudiesHuman medicine030217 neurology & neurosurgery
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The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance : Evidence of validity

2014

BackgroundAn international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.MethodsFourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.ResultsThe agreement among tracers was relatively low…

MalePathologyDiagnostic criteriaEpidemiologyImage Processinggenetics [Alzheimer Disease]HippocampusFunctional LateralityImagingpathology [Alzheimer Disease]ddc:616.89methods [Magnetic Resonance Imaging]Computer-AssistedClinical trialsddc:150methods [Image Processing Computer-Assisted]ValidationImage Processing Computer-AssistedSegmentationHARPmedicine.diagnostic_testHealth PolicyOrgan SizeAlzheimer's diseaseMiddle Agedinstrumentation [Magnetic Resonance Imaging]Manual segmentationMagnetic Resonance ImagingPsychiatry and Mental healthMagnetic resonanceBiomedical ImagingManual segmentationFemalemethods [Neuroimaging]methods [Imaging Three-Dimensional]EADC-ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Volumetry and for the Alzheimer's Disease Neuroimaging Initiativemedicine.medical_specialtyHippocampal volumetry; Magnetic resonance; Alzheimer's disease; Biomarkers; Diagnostic criteria; Enrichment; Clinical trials; Validation; Harmonized protocol; Standard operating procedures; Manual segmentationConcurrent validityClinical SciencesHarmonized protocolNeuroimagingArticleHippocampal volumetryCellular and Molecular NeuroscienceImaging Three-DimensionalDevelopmental NeuroscienceNeuroimagingClinical ResearchAlzheimer DiseasemedicineHumansddc:610AgedProtocol (science)ReproducibilityInternetbusiness.industryNeurosciencesReproducibility of ResultsMagnetic resonance imagingBrain DisordersStandard operating procedurespathology [Hippocampus]EnrichmentGeriatricsThree-DimensionalNeurology (clinical)Geriatrics and GerontologyAtrophyNuclear medicinebusinessBiomarkers
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