AbstractBackgroundAlteration in glycosphingolipids (GSLs) in Parkinson's disease (PD) still needs to be determined.ObjectivesWe evaluated if PD subjects show abnormal GSLs levels compared to healthy controls (HC) and if GSLs correlate with clinical features.MethodsWe analyzed GSLs and glucosylceramide (GlcCer) in plasma using two normal‐phase high‐performance liquid chromatography assays; clinico‐demographic data were extracted.ResultsEighty PD subjects and 25 HCs were analyzed. Levels of GlcCer, GD1b, Gb4, GalNAcGA1, and b‐series were higher in PD patients than in HCs; total GSLs, GT1b, GM1a, GM3, GM2, and a‐series levels were lower in PD patients than in HCs. Changes in GSLs were present in PD subjects, with GlcCer levels similar to those in HCs. The results were similar after excluding certainGBA1mutation carriers. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III, correlated with Gb4 and Montreal Cognitive Assessment with GD1b levels.ConclusionsMultiple GSL abnormalities in plasma were detected in patients with and without GlcCer changes, indicating a broader shift in lipid homeostasis. © 2022 The Authors.Movement Disorderspublished by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.