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Heijer, J.M. den; Cullen, V.C.; Pereira, D.R.; Yavuz, Y.; Kam, M.L. de; Grievink, H.W.; ... ; Groeneveld, G.J.
2023
A biomarker study in patients with GBA1-parkinson's disease and healthy controls
Article / Letter to editor
open access
BackgroundMolecules related to glucocerebrosidase (GCase) are potential biomarkers for development of compounds targeting
GBA1
-associated Parkinson's disease (GBA-PD).ObjectivesAssessing...
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BackgroundMolecules related to glucocerebrosidase (GCase) are potential biomarkers for development of compounds targeting
GBA1
-associated Parkinson's disease (GBA-PD).ObjectivesAssessing variability of various glycosphingolipids (GSLs) in plasma, peripheral blood mononuclear cells (PBMCs), and cerebrospinal fluid (CSF) across GBA-PD, idiopathic PD (iPD), and healthy volunteers (HVs).MethodsData from five studies were combined. Variability was assessed of glucosylceramide (various isoforms), lactosylceramide (various isoforms), glucosylsphingosine, galactosylsphingosine, GCase activity (using fluorescent 4-methylumbeliferryl-β-glucoside), and GCase protein (using enzyme-linked immunosorbent assay) in plasma, PBMCs, and CSF if available, in GBA-PD, 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 – Unified Parkinson's Disease Rating Scale Part 3 [MDS-UPDRS-3], Mini-Mental State Examination [MMSE],
GBA1
mutation type), and participant status (GBA-PD, iPD, HVs).ResultsWithin-subject between-day 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-PD 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.
GBA1
mutation types could not be differentiated based on GSL data.ConclusionsGlucosylceramide can stably be measured over days in both plasma and PBMCs and may be used as a biomarker in clinical trials targeting GBA-PD. Glucosylsphingosine and lactosylceramide are stable in plasma but are strongly affected by leukocyte subtypes in PBMCs. GBA-PD could be differentiated from iPD and HVs, primarily based on glucosylceramide levels in plasma. © 2023 The Authors.
Movement Disorders
published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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