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Substantial progress has been made in identifying positron emission tomography and cerebrospinal fluid biomarkers for AD, but they have limited use as front\u2010line\u00a0diagnostic tools.<\/jats:p>\n                  <jats:p>Extracellular vesicles (EVs) are released by all cells\u00a0and contain a\u00a0subset of their parental cell\u00a0composition, including lipids. EVs are released from the brain into the periphery, providing a potential source of tissue and disease specific lipid biomarkers. However, the EV lipidome of the central nervous system is currently unknown and the potential of brain\u2010derived EVs (BDEVs) to inform on lipid dyshomeostasis in AD remains unclear.<\/jats:p>\n                  <jats:p>The aim of this study was to reveal the lipid composition of BDEVs in human frontal cortex,\u00a0and to determine whether BDEVs\u00a0have an altered lipid profile\u00a0in AD.\u00a0Using semi\u2010quantitative mass spectrometry, we describe the BDEV lipidome, covering four lipid categories, 17 lipid classes and 692 lipid molecules.\u00a0BDEVs were enriched in glycerophosphoserine (PS) lipids, a characteristic of small EVs. Here we further report that BDEVs are enriched in ether\u2010containing PS lipids, a finding that further establishes ether lipids as a feature of EVs.<\/jats:p>\n                  <jats:p>BDEVs in the AD frontal cortex\u00a0offered improved detection of dysregulated lipids in AD over global lipid profiling of this\u00a0brain region.\u00a0 AD BDEVs had significantly altered glycerophospholipid\u00a0and sphingolipid\u00a0levels, specifically increased plasmalogen glycerophosphoethanolamine\u00a0and decreased polyunsaturated fatty acyl containing lipids, and altered amide\u2010linked acyl chain content in sphingomyelin\u00a0and ceramide\u00a0lipids relative to CTL. The most prominent alteration was a two\u2010fold decrease in lipid species containing anti\u2010inflammatory\/pro\u2010resolving docosahexaenoic acid.<\/jats:p>\n                  <jats:p>The in\u2010depth lipidome analysis provided in this study highlights the advantage of EVs over more complex tissues for improved detection of dysregulated lipids that may serve as potential biomarkers in the periphery.<\/jats:p>","DOI":"10.1002\/jev2.12089","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T10:06:35Z","timestamp":1620727595000},"source":"Crossref","is-referenced-by-count":179,"title":["Characterization of brain\u2010derived extracellular vesicle lipids in Alzheimer's disease"],"prefix":"10.1002","volume":"10","author":[{"given":"Huaqi","family":"Su","sequence":"first","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"},{"name":"Department of Biochemistry and Pharmacology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yepy H.","family":"Rustam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin L.","family":"Masters","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enes","family":"Makalic","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona A.","family":"McLean","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Genetics La Trobe Institute for Molecular Science, La Trobe University  Bundoora Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Barnham","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin E.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology The University of Melbourne  Parkville Victoria Australia"},{"name":"School of Chemistry, Bio21 Molecular Science and Biotechnology Institute The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Vella","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"},{"name":"Department of Surgery, The Royal Melbourne Hospital The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3233\/JAD-170035","article-title":"Discovery and confirmation of diagnostic serum lipid biomarkers for Alzheimer\u2019s disease using direct infusion mass spectrometry","volume":"59","author":"Anand S.","year":"2017","journal-title":"Journal of Alzheimer's Disease"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.07.024"},{"key":"e_1_2_6_4_1","first-page":"619","article-title":"Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology","volume":"11","author":"Barupal D. 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