Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases

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Abstract

Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.

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Most cited references 66

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Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Clotilde Théry, Kenneth W Witwer, Elena Aikawa … (2019)

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

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The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Guy M McKhann, David S. Knopman, Howard Chertkow … (2011)

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.

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Extracellular vesicles: Exosomes, microvesicles, and friends

Graça Raposo, Willem Stoorvogel (2013)

Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.

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Author and article information

Contributors

Ana Lloret: Role: Academic Editor

Ana Cervera: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 08 March 2021

Publication date Collection: March 2021

Volume: 22

Issue: 5

Electronic Location Identifier: 2737

Affiliations

[1 ]Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy; daisy.sproviero@ 123456mondino.it (D.S.); stella.gagliardi@ 123456mondino.it (S.G.); szucca@ 123456engenome.com (S.Z.); marta.giannini@ 123456mondino.it (M.G.); maria.garofalo@ 123456mondino.it (M.G.); orietta.pansarasa@ 123456mondino.it (O.P.)

[2 ]EnGenome SRL, 27100 Pavia, Italy

[3 ]Department of Molecular Biotechnology and Health Sciences, Bioinformatics and Genomics Unit, University of Turin, 10126 Turin, Italy; maddalena.arigoni@ 123456unito.it (M.A.); raffaele.calogero@ 123456unito.it (R.A.C.)

[4 ]Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy; alfredo.costa@ 123456mondino.it

[5 ]Department of Biology and Biotechnology (“L. Spallanzani”), University of Pavia, 27100 Pavia, Italy

[6 ]Department of Oncology, University of Turin, 10060 Turin, Italy; martina.olivero@ 123456ircc.it

[7 ]Departments of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA; micheladellorco@ 123456salud.unm.edu

[8 ]Immunohematological and Transfusional Service and Centre of Transplantation Immunology, IRCCS “San Matteo Foundation”, 27100 Pavia, Italy; s.bernuzzi@ 123456sanmatteo.pv.it

[9 ]Neurorehabilitation Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy; micol.avenali@ 123456mondino.it

[10 ]Unit of Behavioral Neurology, IRCCS Mondino Foundation, 27100 Pavia, Italy; matteo.cottaramusino@ 123456mondino.it (M.C.R.); giulia.perini@ 123456mondino.it (G.P.); mauro.ceroni@ 123456mondino.it (M.C.)

[11 ]Neuro-Oncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy; luca.diamanti@ 123456mondino.it

[12 ]Parkinson Unit and Movement Disorders Mondino Foundation IRCCS, 27100 Pavia, Italy; brigida.minafra@ 123456mondino.it (B.M.); roberta.zangaglia@ 123456mondino.it (R.Z.)

[13 ]Departments of Neurosciences and Psychiatry and Behavioral Health, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA; NBizzozero@ 123456salud.unm.edu

Author notes

[* ]Correspondence: cristina.cereda@ 123456mondino.it ; Tel.: +39-0382380348

[†]

These authors have equally contributed to this work.

Author information

Daisy Sproviero https://orcid.org/0000-0001-5061-683X

Stella Gagliardi https://orcid.org/0000-0002-6589-6907

Michela Dell’Orco https://orcid.org/0000-0002-0742-7037

Orietta Pansarasa https://orcid.org/0000-0002-3041-0612

Matteo Cotta Ramusino https://orcid.org/0000-0003-3090-9648

Alfredo Costa https://orcid.org/0000-0001-7312-8011

Raffaele A. Calogero https://orcid.org/0000-0002-2848-628X

Article

Publisher ID: ijms-22-02737

DOI: 10.3390/ijms22052737

PMC ID: 7962970

PubMed ID: 33800495

SO-VID: 9d208288-d73f-4699-ac0f-e20f50f370c3

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases

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Abstract

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Higher order chromatin architecture

Most cited references 66

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Extracellular vesicles: Exosomes, microvesicles, and friends

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