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HO\u20101 does not contain an N\u2010terminal signal peptide and the mechanism responsible for its secretion remains unknown. Extracellular vesicles (EVs) are membrane\u2010bound inclusions that transport microRNAs, messenger RNAs, lipids, and proteins among diverse cellular and extracellular compartments. The objective of the current study was to determine whether EVs in human biofluids contain HO\u20101, and whether the latter may be transported in EVs from brain to periphery. Total, L1 cell adhesion molecule protein (L1CAM)\u2010enriched (neuron\u2010derived), and glutamate aspartate transporter 1 (GLAST)\u2010enriched (astrocyte\u2010derived) EVs were purified from five different human biofluids (saliva [<jats:italic>n<\/jats:italic>\u00a0=\u00a040], plasma [<jats:italic>n<\/jats:italic>\u00a0=\u00a014], serum [<jats:italic>n<\/jats:italic>\u00a0=\u00a010], urine [<jats:italic>n<\/jats:italic>\u00a0=\u00a010], and cerebrospinal fluid [<jats:italic>n<\/jats:italic>\u00a0=\u00a011]) using polymer precipitation and immuno\u2010affinity\u2010based capture methods. L1CAM\u2010enriched, GLAST\u2010enriched, and L1CAM\/GLAST\u2010depleted (LGD) EV, along with EV\u2010depleted (EVD), fractions were validated by nanoparticle tracking analysis, enzyme\u2010linked immunosorbent assay (ELISA), and western blot. HO\u20101 was assayed in all fractions using ELISA and western blot. The majority of HO\u20101 protein was localized to LGD, L1CAM\u2010enriched, and GLAST\u2010enriched EVs of all human biofluids surveyed after adjusting for age and sex, with little HO\u20101 protein detected in EVD fractions. HO\u20101 protein in human biofluids is predominantly localized to EV compartments. A substantial proportion of EV HO\u20101 in peripheral human biofluids is derived from the central nervous system and may contribute to the systemic manifestations of various neurological conditions.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15167-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15167","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T13:57:45Z","timestamp":1599141465000},"page":"2195-2209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Characterization and heme oxygenase\u20101 content of extracellular vesicles in human biofluids"],"prefix":"10.1111","volume":"157","author":[{"given":"Marisa","family":"Cressatti","sequence":"first","affiliation":[{"name":"Lady Davis Institute for Medical Research Jewish General Hospital Montreal QC Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"Galindez","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research Jewish General Hospital Montreal QC Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamin","family":"Juwara","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research Jewish General Hospital Montreal QC Canada"},{"name":"Quantitative Life Sciences McGill University Montreal QC 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