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

作     者：Ana Gámez-Valero Jaume Campdelacreu Dolores Vilas Lourdes Ispierto Ramón Reñé RamiroÁlvarez MPilar Armengol Francesc E.Borràs Katrin Beyer 

作者机构：Department of PathologyHealth Sciences Research Institute Germans Trias i Pujol(IGTP)Universitat Autònoma de BarcelonaBadalona 08916Spain REMAR-IVECAT groupHealth Sciences Research Institute Germans Trias i Pujol(IGTP)08916 BadalonaSpain Department of NeurologyHospital Universitari de BellvitgeL’Hospitalet de Llobregat 08907Spain Department of NeurologyHospital Universitari Germans Trias i Pujol08916 BadalonaSpain Genomic and Microscopy facilitiesHealth Sciences Research Institute Germans Trias i Pujol(IGTP)08916 BadalonaSpain Department of Cell BiologyPhysiology and ImmunologyUniversitat Autònoma de Barcelona(UAB)BarcelonaSpain 

出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)

年 卷 期：2019年第8卷第1期

页      面：382-398页

核心收录：

学科分类：0710[理学-生物学] 0402[教育学-心理学(可授教育学、理学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 1010[医学-医学技术（可授医学、理学学位）] 100214[医学-肿瘤学] 1009[医学-特种医学] 10[医学] 

基　　金：This work was supported by Spain’s Ministry of Health,project PI18/00276,integrated in the National R+D+I and funded by the ISCIII and the European Regional Development Fund This work was also supported by the MaratóTV3 grant 201405/10 

主　　题：Neurodegenerative disorders Biomarker Exosomes Next generation sequencing Extracellular vesicles 

摘      要：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.