{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:01:46Z","timestamp":1790708506923,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Molecules related to glucocerebrosidase (GCase) are potential biomarkers for development of compounds targeting\n                      <jats:italic>GBA1<\/jats:italic>\n                      \u2010associated Parkinson's disease (GBA\u2010PD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Assessing variability of various glycosphingolipids (GSLs) in plasma, peripheral blood mononuclear cells (PBMCs), and cerebrospinal fluid (CSF) across GBA\u2010PD, idiopathic PD (iPD), and healthy volunteers (HVs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from five studies were combined. Variability was assessed of glucosylceramide (various isoforms), lactosylceramide (various isoforms), glucosylsphingosine, galactosylsphingosine, GCase activity (using fluorescent 4\u2010methylumbeliferryl\u2010\u03b2\u2010glucoside), and GCase protein (using enzyme\u2010linked immunosorbent assay) in plasma, PBMCs, and CSF if available, in GBA\u2010PD, iPD, and HVs. GSLs in leukocyte subtypes were compared in HVs. Principal component analysis was used to explore global patterns in GSLs, clinical characteristics (Movement Disorder Society \u2013 Unified Parkinson's Disease Rating Scale Part 3 [MDS\u2010UPDRS\u20103], Mini\u2010Mental State Examination [MMSE],\n                      <jats:italic>GBA1<\/jats:italic>\n                      mutation type), and participant status (GBA\u2010PD, iPD, HVs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Within\u2010subject between\u2010day variability ranged from 5.8% to 44.5% and was generally lower in plasma than in PBMCs. Extracellular glucosylceramide levels (plasma) were slightly higher in GBA\u2010PD compared with both iPD and HVs, while intracellular levels were comparable. GSLs in the different matrices (plasma, PBMCs, CSF) did not correlate. Both lactosylceramide and glucosylsphingosine were more abundant in granulocytes compared with monocytes and lymphocytes. Absolute levels of GSL isoforms differed greatly.\n                      <jats:italic>GBA1<\/jats:italic>\n                      mutation types could not be differentiated based on GSL data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Glucosylceramide can stably be measured over days in both plasma and PBMCs and may be used as a biomarker in clinical trials targeting GBA\u2010PD. Glucosylsphingosine and lactosylceramide are stable in plasma but are strongly affected by leukocyte subtypes in PBMCs. GBA\u2010PD could be differentiated from iPD and HVs, primarily based on glucosylceramide levels in plasma. \u00a9 2023 The Authors.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.29360","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T07:39:18Z","timestamp":1678779558000},"page":"783-795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A Biomarker Study in Patients with\n                    <i>GBA1<\/i>\n                    \u2010Parkinson's Disease and Healthy Controls"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-7978","authenticated-orcid":false,"given":"Jonas M.","family":"den Heijer","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie C.","family":"Cullen","sequence":"additional","affiliation":[{"name":"Lysosomal Therapeutics Inc.  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