{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:17:36Z","timestamp":1792113456550,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1ZIA\u2010AG000546"],"award-info":[{"award-number":["1ZIA\u2010AG000546"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["MJFF\u2010020700"],"award-info":[{"award-number":["MJFF\u2010020700"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p><jats:italic>GBA1<\/jats:italic> variants and decreased glucocerebrosidase activity are implicated in Parkinson's disease (PD). We investigated the hypothesis that increased levels of glucosylceramide (GlcCer), a main substrate of glucocerebrosidase, are involved in PD pathogenesis. Using multiple genetic methods, we show that ATPase phospholipid transporting 10D (<jats:italic>ATP10D<\/jats:italic>), not <jats:italic>GBA1<\/jats:italic>, is the main regulator of plasma GlcCer levels, yet it is not involved in PD pathogenesis. Plasma GlcCer levels were associated with PD, but not in a causative manner, and are not predictive of disease status. These results argue against targeting GlcCer in <jats:italic>GBA1<\/jats:italic>\u2010PD, and underscore the need to explore alternative mechanisms and biomarkers for PD. ANN NEUROL 2025;97:873\u2013878<\/jats:p>","DOI":"10.1002\/ana.27219","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:34:37Z","timestamp":1741743277000},"page":"873-878","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Plasma Glucosylceramide Levels Are Regulated by <scp><i>ATP10D<\/i><\/scp> and Are Not Involved in Parkinson's Disease Pathogenesis"],"prefix":"10.1002","volume":"97","author":[{"given":"Emma N.","family":"Somerville","sequence":"first","affiliation":[{"name":"The Neuro (Montr\u00e9al Neurological Institute\u2010Hospital) McGill University  Montr\u00e9al QC Canada"},{"name":"Department of Human Genetics McGill University  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alva","family":"James","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beetz","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Schwieger","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gal","family":"Barrel","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna K.","family":"Kandaswamy","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius I.","family":"Iurascu","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bauer","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ta","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics National Institute on Aging, National Institutes of Health  Bethesda MD USA"},{"name":"DataTecnica International  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Iwaki","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics National Institute on Aging, National Institutes of Health  Bethesda MD USA"},{"name":"DataTecnica International  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3407-5716","authenticated-orcid":false,"given":"Konstantin","family":"Senkevich","sequence":"additional","affiliation":[{"name":"The Neuro (Montr\u00e9al Neurological Institute\u2010Hospital) McGill University  Montr\u00e9al QC Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-4564","authenticated-orcid":false,"given":"Eric","family":"Yu","sequence":"additional","affiliation":[{"name":"The Neuro (Montr\u00e9al Neurological Institute\u2010Hospital) McGill University  Montr\u00e9al QC Canada"},{"name":"Department of Human Genetics McGill University  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy N.","family":"Alcalay","sequence":"additional","affiliation":[{"name":"Department of Neurology Columbia University Irving Medical Center  New York NY USA"},{"name":"Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-234X","authenticated-orcid":false,"given":"Ziv","family":"Gan\u2010Or","sequence":"additional","affiliation":[{"name":"The Neuro (Montr\u00e9al Neurological Institute\u2010Hospital) McGill University  Montr\u00e9al QC Canada"},{"name":"Department of Human Genetics McGill University  Montr\u00e9al QC Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29314"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00283-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-018-0860-4"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv179"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-024-00779-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz350"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25629"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.06.001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0339-z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.09.015"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28472"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29163"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2007.11.004"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00205-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2213"},{"key":"e_1_2_9_19_1","volume-title":"R: a language and environment for statistcal computing","author":"R Development Core Team","year":"2023"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30320-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2024.100508"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000672"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073094"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.27219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:39:58Z","timestamp":1759135198000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.27219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/ana.27219"],"URL":"https:\/\/doi.org\/10.1002\/ana.27219","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2024-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}