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Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson's Disease
Author(s) -
Surface Matthew,
Balwani Manisha,
Waters Cheryl,
Haimovich Alexander,
GanOr Ziv,
Marder Karen S.,
Hsieh Tammy,
Song Linxia,
Padmanabhan Shalini,
Hsieh Frank,
Merchant Kalpana M.,
Alcalay Roy N.
Publication year - 2022
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28846
Subject(s) - glucocerebrosidase , heterozygote advantage , biomarker , compound heterozygosity , disease , parkinson's disease , pathogenesis , chemistry , medicine , mutation , genotype , gene , biochemistry
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.