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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\u2019s disease (AD), Parkinson\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms22052737","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T23:04:39Z","timestamp":1615244679000},"page":"2737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-683X","authenticated-orcid":false,"given":"Daisy","family":"Sproviero","sequence":"first","affiliation":[{"name":"Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6589-6907","authenticated-orcid":false,"given":"Stella","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Zucca","sequence":"additional","affiliation":[{"name":"Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"EnGenome SRL, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Arigoni","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Bioinformatics and Genomics Unit, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Giannini","sequence":"additional","affiliation":[{"name":"Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Garofalo","sequence":"additional","affiliation":[{"name":"Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Biology and Biotechnology (\u201cL. Spallanzani\u201d), University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Olivero","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Turin, 10060 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0742-7037","authenticated-orcid":false,"given":"Michela","family":"Dell\u2019Orco","sequence":"additional","affiliation":[{"name":"Departments of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3041-0612","authenticated-orcid":false,"given":"Orietta","family":"Pansarasa","sequence":"additional","affiliation":[{"name":"Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bernuzzi","sequence":"additional","affiliation":[{"name":"Immunohematological and Transfusional Service and Centre of Transplantation Immunology, IRCCS \u201cSan Matteo Foundation\u201d, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Avenali","sequence":"additional","affiliation":[{"name":"Neurorehabilitation Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3090-9648","authenticated-orcid":false,"given":"Matteo","family":"Cotta Ramusino","sequence":"additional","affiliation":[{"name":"Unit of Behavioral Neurology, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Diamanti","sequence":"additional","affiliation":[{"name":"Neuro-Oncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigida","family":"Minafra","sequence":"additional","affiliation":[{"name":"Parkinson Unit and Movement Disorders Mondino Foundation IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Perini","sequence":"additional","affiliation":[{"name":"Unit of Behavioral Neurology, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Zangaglia","sequence":"additional","affiliation":[{"name":"Parkinson Unit and Movement Disorders Mondino Foundation IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-8011","authenticated-orcid":false,"given":"Alfredo","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Unit of Behavioral Neurology, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Ceroni","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Unit of Behavioral Neurology, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora I.","family":"Perrone-Bizzozero","sequence":"additional","affiliation":[{"name":"Departments of Neurosciences and Psychiatry and Behavioral Health, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2848-628X","authenticated-orcid":false,"given":"Raffaele A.","family":"Calogero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Bioinformatics and Genomics Unit, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9571-0862","authenticated-orcid":false,"given":"Cristina","family":"Cereda","sequence":"additional","affiliation":[{"name":"Genomic and post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1242\/dmm.030205","article-title":"Neurodegenerative disease: Models, mechanisms, and a new hope","volume":"10","author":"Gitler","year":"2017","journal-title":"Dis. 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