{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:29:35Z","timestamp":1792045775357,"version":"4.4.0"},"reference-count":90,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK (ARUK)","doi-asserted-by":"publisher","award":["ARUK-PPG2018A-009"],"award-info":[{"award-number":["ARUK-PPG2018A-009"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: Systemic infection is associated with increased neuroinflammation and accelerated cognitive decline in AD patients. Activated neutrophils produce neutrophil-derived microvesicles (NMV), which are internalised by human brain microvascular endothelial cells and increase their permeability in vitro, suggesting that NMV play a role in blood\u2013brain barrier (BBB) integrity during infection. The current study investigated whether microRNA content of NMV from AD patients is significantly different compared to healthy controls and could impact cerebrovascular integrity. (2) Methods: Neutrophils isolated from peripheral blood samples of five AD and five healthy control donors without systemic infection were stimulated to produce NMV. MicroRNAs isolated from NMV were analysed by RNA-Seq, and online bioinformatic tools were used to identify significantly differentially expressed microRNAs in the NMV. Target and pathway analyses were performed to predict the impact of the candidate microRNAs on vascular integrity. (3) Results: There was no significant difference in either the number of neutrophils (p = 0.309) or the number of NMV (p = 0.3434) isolated from AD donors compared to control. However, 158 microRNAs were significantly dysregulated in AD NMV compared to controls, some of which were associated with BBB dysfunction, including miR-210, miR-20b-5p and miR-126-5p. Pathway analysis revealed numerous significantly affected pathways involved in regulating vascular integrity, including the TGF\u03b2 and PDGFB pathways, as well as Hippo, IL-2 and DNA damage signalling. (4) Conclusions: NMV from AD patients contain miRNAs that may alter the integrity of the BBB and represent a novel neutrophil-mediated mechanism for BBB dysfunction in AD and the accelerated cognitive decline seen as a result of a systemic infection.<\/jats:p>","DOI":"10.3390\/ijms23115913","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T08:41:33Z","timestamp":1653468093000},"page":"5913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["RNA-Seq Profiling of Neutrophil-Derived Microvesicles in Alzheimer\u2019s Disease Patients Identifies a miRNA Signature That May Impact Blood\u2013Brain Barrier Integrity"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1668-7797","authenticated-orcid":false,"given":"Irina","family":"V\u00e1zquez-Villase\u00f1or","sequence":"first","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia I.","family":"Smith","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung J. R.","family":"Thang","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-1438","authenticated-orcid":false,"given":"Paul R.","family":"Heath","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Wharton","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8886-1283","authenticated-orcid":false,"given":"Daniel J.","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria C.","family":"Ridger","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity and Cardiovascular Disease, Medical School, The University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-4271","authenticated-orcid":false,"given":"Julie E.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield S10 2HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S303","DOI":"10.1016\/S0197-4580(04)80997-7","article-title":"P2-251 Association between dementia and systemic infectious disease: Evidence from a case-control study","volume":"25","author":"Holmes","year":"2004","journal-title":"Neurobiol. 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