{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T06:39:17Z","timestamp":1777185557657,"version":"3.51.4"},"reference-count":84,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["isevjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Bio"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Niemann\u2010Pick disease type C (NPC) is a rare neurodegenerative disease primarily caused by mutations in the\n                    <jats:italic>NPC1<\/jats:italic>\n                    gene, which is associated with cholesterol trafficking impairment, and disruption of endolysosomal processing and extracellular vesicles (EVs). Here, for patients with\n                    <jats:italic>NPC1<\/jats:italic>\n                    mutations (NPC) and age\u2010matched controls (CTL) we describe the EV profile of dermal fibroblasts (\n                    <jats:italic>n<\/jats:italic>\n                    = 5 NPC,\n                    <jats:italic>n<\/jats:italic>\n                    = 3 CTL) and, for the first time, cerebrospinal fluid (CSF,\n                    <jats:italic>n<\/jats:italic>\n                    = 5 NPC,\n                    <jats:italic>n<\/jats:italic>\n                    = 5 CTL). EVs were enriched using size\u2010exclusion chromatography and characterized by immunoblot, transmission electron microscopy, and microchip resistive pulse sensing. Single vesicle flow cytometry showed increased EV concentration in NPC CSF versus CTLs. In fibroblasts, EV concentration inversely correlated with NPC1 protein levels that was partially attenuated by hydroxypropyl\u2010\u03b2\u2010cyclodextrin, an experimental NPC therapeutic. Direct stochastic imaging and multiplexed EV immunoassays revealed that NPC EVs were enriched for endolysosomal proteins (CD63, Lamp1). Three miRNAs (miR\u2010365\u20103p, \u2010654\u20103p, \u2010598\u20103p) were increased in NPC fibroblast EVs and two (miR\u2010320a, \u2010199a\/b\u20103p) in NPC CSF EVs. Pathway analysis using those miRNAs identified relevant diseases and functions (cell death and survival, molecular transport, heredity neurological disease). These results demonstrate that\n                    <jats:italic>NPC1<\/jats:italic>\n                    gene mutations alter EV biogenesis and disease\u2010associated changes in cargo that may serve as clinical biomarkers or therapeutic targets for NPC, a devastating disease without a cure.\n                  <\/jats:p>","DOI":"10.1002\/jex2.70136","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T12:47:26Z","timestamp":1776430046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of Extracellular Vesicle Concentration, MicroRNAs, and Surface Proteins in Patients With Niemann\u2010Pick Disease Type C"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-522X","authenticated-orcid":false,"given":"Sarah Catherine BB","family":"Hawthorne","sequence":"first","affiliation":[{"name":"Department of Anesthesiology &amp; Perioperative Medicine Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3646-7089","authenticated-orcid":false,"given":"Ursula S","family":"Sandau","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Perioperative Medicine Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-4930","authenticated-orcid":false,"given":"Trevor J","family":"McFarland","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Perioperative Medicine Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-1522","authenticated-orcid":false,"given":"Elizabeth","family":"Berry\u2010Kravis","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neurological Sciences, &amp; Anatomy\/Cell Biology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2996-9611","authenticated-orcid":false,"given":"Julie A","family":"Saugstad","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Perioperative Medicine Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264\u2010024\u201001183\u20105"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202006178"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.994080"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2021.100879"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.12.014"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.78038"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.78038"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.02.004"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2024.02.004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28463"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201300350"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126600"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5323.228"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cdn\/nzab033_005"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220007"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227829"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015054"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz757"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071763"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12144"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.023"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jex2.40"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070727"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2016.05.001"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.RA119000571"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010018\u20100785\u20107"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11040576"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1086\/302620"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010019\u20101617\u2010y"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs20100297"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202101055"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S291956"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.20517\/evcna.2022.41"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1079"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2021.158916"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.70029"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1426180"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010024\u201002459\u2010w"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202105060"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.57125"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.720778"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010018\u20101422\u20100"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158146"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201024384\u20102"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2016_41"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1086\/302626"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106769"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13061034"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.11.026"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63970"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010024\u201001432\u20109"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010021\u201001719\u20102"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24050994"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077251"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.wad.0000194014.43575.fd"},{"issue":"35","key":"e_1_2_9_58_1","article-title":"Restoration of Cholesterol Trafficking resultsin Decreased Markers of Neuronal Damage in Individuals With Niemann\u2010Pick Disease Type C1","volume":"98","author":"Porter F. D.","year":"2025","journal-title":"Annals of Neurology"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010440"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2010.06976.x"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.20517\/evcna.2024.92"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12028"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12397"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.864022"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201052681\u20105"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010200396"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232\u2010014\u20109761\u2010x"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/jex2.115"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22311"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910794"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106141"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.134775"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1535750"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113116"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.04.017"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.757482"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20105\u201016"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020710"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1713526"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14895"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010180539"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01326"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.048929"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1330400"}],"container-title":["Journal of Extracellular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jex2.70136","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jex2.70136","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jex2.70136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T05:54:20Z","timestamp":1777182860000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jex2.70136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":84,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/jex2.70136"],"URL":"https:\/\/doi.org\/10.1002\/jex2.70136","archive":["Portico"],"relation":{},"ISSN":["2768-2811","2768-2811"],"issn-type":[{"value":"2768-2811","type":"print"},{"value":"2768-2811","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2026-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70136"}}