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Furthermore, there are no current methods to ascertain the progression and conversion of prodromal conditions such as REM behaviour disorder (RBD). Extracellular vesicles (EVs), containing a mixture of biomolecules, have emerged as potential sources for parkinsonian diagnostics. However, inconsistencies in previous studies have left their diagnostic potential unclear. We conducted a meta\u2010analysis, following PRISMA guidelines, to assess the diagnostic accuracy of general EVs isolated from various bodily fluids, including cerebrospinal fluid (CSF), plasma, serum, urine or saliva, in differentiating patients with parkinsonian disorders from healthy controls (HCs). The meta\u2010analysis included 21 studies encompassing 1285 patients with PD, 24 with MSA, 105 with DLB, 99 with PSP, 101 with RBD and 783 HCs. Further analyses were conducted only for patients with PD versus HCs, given the limited number for other comparisons. Using bivariate and hierarchal receiver operating characteristics (HSROC) models, the meta\u2010analysis revealed moderate diagnostic accuracy in distinguishing patients with PD from HCs, with substantial heterogeneity and publication bias. The trim\u2010and\u2010fill method revealed at least two missing studies with null or low diagnostic accuracy. CSF\u2010EVs showed better overall diagnostic accuracy, while plasma\u2010EVs had the lowest performance. General EVs demonstrated higher diagnostic accuracy compared to CNS\u2010originating EVs, which are more time\u2010consuming, labour\u2010 and cost\u2010intensive to isolate. In conclusion, while holding promise, utilizing biomarkers in general EVs for PD diagnosis remains unfeasible due to existing challenges. The focus should shift toward harmonizing the field through standardization, collaboration, and rigorous validation. Current efforts by the International Society For Extracellular Vesicles (ISEV)\u00a0aim to enhance the accuracy and reproducibility of EV\u2010related research through rigor and standardization, aiming to bridge the gap between theory and practical clinical application.<\/jats:p>","DOI":"10.1002\/jex2.121","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T05:58:48Z","timestamp":1699855128000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Extracellular vesicles from bodily fluids for the accurate diagnosis of Parkinson's disease and related disorders: A systematic review and diagnostic meta\u2010analysis"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3056-8878","authenticated-orcid":false,"given":"Hash Brown","family":"Taha","sequence":"first","affiliation":[{"name":"Department of Integrative Biology &amp; Physiology University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Bogoniewski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, David Geffen School of Medicine University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105185"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.4304"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010019\u201000751\u2010y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24736"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1353\u20108020(11)70029\u20103"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg C. 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