Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer's disease and dementia with Lewy bodies
Gámez-Valero, Ana (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Campdelacreu, Jaume (Hospital Universitari de Bellvitge)
Vilas, Dolores (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ispierto, Lourdes (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Reñé, Ramón (Hospital Universitari de Bellvitge)
Álvarez, Ramiro (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Armengol Barnils, Maria del Pilar (Institut Germans Trias i Pujol)
Borràs i Serres, Francesc Enric (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Beyer, Katrin (Institut Germans Trias i Pujol)

Fecha:	2019
Resumen:	Because of the increasing life expectancy in our society, aging-related neurodegenerative disorders are one of the main issues in global health. Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline. Among these diseases, Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common types of degenerative dementia. Although both show specific features, an important neuropathological and clinical overlap between them hampers their correct diagnosis. In this work, we identified molecular biomarkers aiming to improve the misdiagnosis between both diseases. 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 microscopy. Next Generation Sequencing (NGS) and related bibliographic search was performed and a selected group of EV-associated microRNAs (miRNAs) was analysed by qPCR. 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 hsa-miR-151a-3p) significantly decreased in AD respect to controls. The 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 diseases. Target 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 others. 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. The online version of this article (10. 1186/s40035-019-0169-5) contains supplementary material, which is available to authorized users.
Ayudas:	Instituto de Salud Carlos III PI18-00276
Nota:	Altres ajuts: This work was also supported by the MaratóTV3 grant 201405/10.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Neurodegenerative disorders ; Biomarker ; Exosomes ; Next generation sequencing ; Extracellular vesicles
Publicado en:	Translational Neurodegeneration, Vol. 8 (october 2019) , ISSN 2047-9158

DOI: 10.1186/s40035-019-0169-5
PMID: 31592314

17 p, 1.4 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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