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

Gámez-Valero, Ana, Campdelacreu, Jaume, Vilas, Dolores, Ispierto, Lourdes, Reñé, Ramón, Álvarez, Ramiro, Armengol, M. Pilar, Borràs, Francesc E., Beyer, Katrin·2019·Translational Neurodegeneration
DOI 10.1186/s40035-019-0169-5PMC PMC6775659
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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.

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Metadata

Authors
Gámez-Valero, A., Campdelacreu, J., Vilas, D., Ispierto, L., Reñé, R., Álvarez, R., Armengol, M. P., Borràs, F. E., & Beyer, K.
Venue
Translational Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2019-10-04
Volume
8
Issue
1
ISSN
2047-9158
DOI
10.1186/s40035-019-0169-5
PMC
PMC6775659
Cited by
167
References
8
Language
en
Licence
Funders
  • Ministry of Science, Innovation and Universities (PI15/00216)
  • Fundació la Marató de TV3 (201405/10)

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