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With this study, we took an in\u2010depth look at the proteome of the (non\u2010purified) cerebrospinal fluid (CSF) and the CSF\u2010derived extracellular vesicles (EVs) of AD, PD, PD\u2010MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label\u2010free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF\u2010derived EV samples (<jats:italic>N<\/jats:italic>\u00a0=\u00a0276) compared to non\u2010purified CSF (<jats:italic>N<\/jats:italic>\u00a0=\u00a0169), with minimal overlap between both datasets. This finding suggests that CSF\u2010derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease\u2010specific markers, we selected a total of 39 biomarker candidates identified in non\u2010purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF\u2010derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease\u2010specific pharmacological therapeutics.<\/jats:p>","DOI":"10.1002\/jev2.12383","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T15:24:27Z","timestamp":1702394667000},"source":"Crossref","is-referenced-by-count":43,"title":["Proteomic comparison between non\u2010purified cerebrospinal fluid and cerebrospinal fluid\u2010derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7810-9303","authenticated-orcid":false,"given":"Yael","family":"Hirschberg","sequence":"first","affiliation":[{"name":"Health Unit Flemish Institute for Technological Research (VITO)  Mol Belgium"},{"name":"Centre for Proteomics (CfP) University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Valle\u2010Tamayo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sant Pau Memory Unit, Sant Pau Biomedical Research Institute Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Dols\u2010Icardo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sant Pau Memory Unit, Sant Pau Biomedical Research Institute Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan","family":"Engelborghs","sequence":"additional","affiliation":[{"name":"Department of Neurology and Bru\u2010BRAIN Universitair Ziekenhuis Brussel and NEUR Research Group, Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB)  Brussels Belgium"},{"name":"Department of Biomedical Sciences University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Buelens","sequence":"additional","affiliation":[{"name":"Data Science Hub, Flemish Institute for Technological Research (VITO)  Mol Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-620X","authenticated-orcid":false,"given":"Roosmarijn E.","family":"Vandenbroucke","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, VIB  Ghent Belgium"},{"name":"Department of Biomedical Molecular Biology Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Vermeiren","sequence":"additional","affiliation":[{"name":"Faculty of Medicine &amp; 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