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

Ana Gámez-Valero; Jaume Campdelacreu; Dolores Vilas; Lourdes Ispierto; Ramón Reñé; Ramiro Álvarez; M Pilar Armengol; Francesc E Borràs; Katrin Beyer

doi:10.1186/s40035-019-0169-5

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

Transl Neurodegener. 2019 Oct 3:8:31. doi: 10.1186/s40035-019-0169-5. eCollection 2019.

Authors

Ana Gámez-Valero^{1

2}, Jaume Campdelacreu³, Dolores Vilas⁴, Lourdes Ispierto⁴, Ramón Reñé³, Ramiro Álvarez⁴, M Pilar Armengol⁵, Francesc E Borràs^#^{2

6}, Katrin Beyer^#¹

Affiliations

¹ 1Department of Pathology, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, Badalona, 08916 Spain.
² 2REMAR-IVECAT group, Health Sciences Research Institute Germans Trias i Pujol (IGTP), 08916 Badalona, Spain.
³ 3Department of Neurology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, 08907 Spain.
⁴ 4Department of Neurology, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain.
⁵ 5Genomic and Microscopy facilities, Health Sciences Research Institute Germans Trias i Pujol (IGTP), 08916 Badalona, Spain.
⁶ 6Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.

^# Contributed equally.

Abstract

Background: 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.

Methods: 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: 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.

Conclusion: 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.

Keywords: Biomarker; Exosomes; Extracellular vesicles; Neurodegenerative disorders; Next generation sequencing.