Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson's Disease

BACKGROUND: Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD).

Glucosylsphingosine is a clinically meaningful biomarker of Gaucher's disease but could not be assayed previously in heterozygous GBA1 carriers.

OBJECTIVE: The aim of this study was to assess plasma glucosylsphingosine levels in GBA1 N370S carriers with and without PD.

METHODS: Glucosylsphingosine, glucosylceramide, and four other lipids were quantified in plasma from N370S heterozygotes with (n = 20) or without (n = 20) PD, healthy controls (n = 20), idiopathic PD (n = 20), and four N370S homozygotes (positive controls; Gaucher's/PD) using quantitative ultra‐performance liquid chromatography tandem mass spectrometry.

RESULTS: Plasma glucosylsphingosine was significantly higher in N370S heterozygotes compared with noncarriers, independent of disease status.

As expected, Gaucher's/PD cases showed increases in both glucocerebrosidase substrates, glucosylsphingosine and glucosylceramide.

CONCLUSIONS: Plasma glucosylsphingosine accumulation in N370S heterozygotes shown in this study opens up its future assessment as a clinically meaningful biomarker of GBA1‐PD.

© 2021 The Authors.

Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.