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Synaptic function is in fact deeply affected in the very early disease phases and recognized as the main cause of AD-related cognitive impairment. While the reciprocal involvement of amyloid beta (A\u03b2) and tau peptides in these processes is under intense investigation, the crucial role of extracellular vesicles (EVs) released by different brain cells as vehicles for these molecules and as mediators of early synaptic alterations is gaining more and more ground in the field. In this review, we will summarize the current literature on the contribution of EVs derived from distinct brain cells to neuronal alterations and build a working model for EV-mediated propagation of synaptic dysfunction in early AD. A deeper understanding of EV\u2013neuron interaction will provide useful targets for the development of novel therapeutic approaches aimed at hampering AD progression.<\/jats:p>","DOI":"10.3390\/cells12010063","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T07:02:12Z","timestamp":1672124532000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Emerging Roles of Extracellular Vesicles in Alzheimer\u2019s Disease: Focus on Synaptic Dysfunction and Vesicle\u2013Neuron Interaction"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4958-541X","authenticated-orcid":false,"given":"Martina","family":"Gabrielli","sequence":"first","affiliation":[{"name":"CNR-Institute of Neuroscience, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1597-2681","authenticated-orcid":false,"given":"Francesca","family":"Tozzi","sequence":"additional","affiliation":[{"name":"Bio@SNS Laboratory, Scuola Normale Superiore, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Verderio","sequence":"additional","affiliation":[{"name":"CNR-Institute of Neuroscience, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-881X","authenticated-orcid":false,"given":"Nicola","family":"Origlia","sequence":"additional","affiliation":[{"name":"CNR-Institute of Neuroscience, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. 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