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Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer’s disease and dementia with Lewy bodies

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Translational Neurodegeneration 2019年第1期8卷 382-398页

作者： Ana Gámez-Valero jaume campdelacreu Dolores Vilas Lourdes Ispierto Ramón Reñé RamiroÁlvarez MPilar Armengol Francesc E.Borràs Katrin Beyer Department of Pathology Health Sciences Research Institute Germans Trias i Pujol(IGTP)Universitat Autònoma de BarcelonaBadalona 08916Spain REMAR-IVECAT group Health Sciences Research Institute Germans Trias i Pujol(IGTP)08916 BadalonaSpain Department of Neurology Hospital Universitari de BellvitgeL’Hospitalet de Llobregat 08907Spain Department of Neurology Hospital Universitari Germans Trias i Pujol08916 BadalonaSpain Genomic and Microscopy facilities Health Sciences Research Institute Germans Trias i Pujol(IGTP)08916 BadalonaSpain Department of Cell Biology Physiology and ImmunologyUniversitat Autònoma de Barcelona(UAB)BarcelonaSpain

Background:Because of the increasing life expectancy in our society,aging-related neurodegenerative disorders are one of the main issues in global *** of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive *** these diseases,Alzheimer’s disease(AD)and dementia with Lewy bodies(DLB)are the most common types of degenerative *** both show specific features,an important neuropathological and clinical overlap between them hampers their correct *** this work,we identified molecular biomarkers aiming to improve the misdiagnosis between both ***:Plasma extracellular vesicles(EVs)-from DLB,AD and healthy controls-were isolated using size-exclusion chromatography(SEC)and characterized by flow cytometry,Nanoparticle Tracking Analysis(NTA)and cryo-electron *** Generation Sequencing(NGS)and related bibliographic search was performed and a selected group of EV-associated microRNAs(miRNAs)was analysed by ***:Results uncovered two miRNAs(hsa-miR-451a and hsa-miR-21-5p)significantly down-regulated in AD samples respect to DLB patients,and a set of four miRNAs(hsa-miR-23a-3p,hsa-miR-126-3p,hsa-let-7i-5p,and hsamiR-151a-3p)significantly decreased in AD respect to *** two miRNAs showing decreased expression in AD in comparison to DLB provided area under the curve(AUC)values of 0.9 in ROC curve analysis,thus suggesting their possible use as biomarkers to discriminate between both *** gene analysis of these miRNAs using prediction online tools showed accumulation of phosphorylation enzymes,presence of proteasome-related proteins and genes involved in cell death among ***:Our data suggest that plasma-EV associated miRNAs may reflect a differential profile for a given dementia-related disorder which,once validated in larger cohorts of patients,could help to improve the differential diagnosis of DLB versus AD.

关键词： Neurodegenerative disorders Biomarker Exosomes Next generation sequencing Extracellular vesicles

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