ArticleNPJ Parkinson's disease2021
Glucosylceramide in cerebrospinal fluid of patients with GBA-associated and idiopathic Parkinson's disease enrolled in PPMI.
Article in NPJ Parkinson's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
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- A Nominally Safe Dose of Fumonisins Induces Mild Neuroinflammation in Chickens by Targeting Sphingolipids and Oxylipins but Not Cytokines.Antioxidants (Basel, Switzerland) · 2026Article
- Age at onset of Parkinson's disease modulates the sphingolipid-dopaminergic interplay in autonomic progression.NPJ Parkinson's disease · 2026Article
- Multi-omics insights into GBA1-associated Parkinson's disease: interplay of genomics, transcriptomics, proteomics, and lipidomics.Molecular neurodegeneration · 2026Review
- Cerebrospinal fluid sphingolipid and sterol metabolite profiles of neurologically normal subjects.Molecular and cellular biochemistry · 2025Article
- Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy.The FEBS journal · 2025Review
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- Application of IVDr NMR spectroscopy to stratify Parkinson's disease with absolute quantitation of blood serum metabolites and lipoproteins.Scientific reports · 2025Article
- Cerebrospinal ceramides and cognition as a function of striatal asymmetry in early stage of Parkinson's disease.Journal of Parkinson's disease · 2025Article
- Review
- Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.Translational neurodegeneration · 2024Review
- Evaluation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Analysis of Glucosylceramide and Galactosylceramide Isoforms in Cerebrospinal Fluid of Parkinson's Disease Patients.Analytical chemistry · 2024Article
- Review
- Neuroimaging and fluid biomarkers in Parkinson's disease in an era of targeted interventions.Nature communications · 2024Review
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons.Aging cell · 2024Article
- Biomarkers for Managing Neurodegenerative Diseases.Biomolecules · 2024Review
- Neuronal progenitor cells-based metabolomics study reveals dysregulated lipid metabolism and identifies putative biomarkers for CLN6 disease.Scientific reports · 2023Article
- Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson's disease.NPJ Parkinson's disease · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Protein-coding variants in the GBA gene modulate susceptibility and progression in ~10% of patients with Parkinson's disease (PD). GBA encodes the β-glucocerebrosidase enzyme that hydrolyzes glucosylceramide. We hypothesized that GBA mutations will lead to glucosylceramide accumulation in cerebrospinal fluid (CSF). Glucosylceramide, ceramide, sphingomyelin, and lactosylceramide levels were measured by liquid chromatography-tandem mass spectrometry in CSF of 411 participants from the Parkinson's Progression Markers Initiative (PPMI) cohort, including early stage, de novo PD patients with abnormal dopamine transporter neuroimaging and healthy controls. Forty-four PD patients carried protein-coding GBA variants (GBA-PD) and 227 carried wild-type alleles (idiopathic PD). The glucosylceramide fraction was increased (P = 0.0001), and the sphingomyelin fraction (a downstream metabolite) was reduced (P = 0.0001) in CSF of GBA-PD patients compared to healthy controls. The ceramide fraction was unchanged, and lactosylceramide was below detection limits. We then used the ratio of glucosylceramide to sphingomyelin (the GlcCer/SM ratio) to explore whether these two sphingolipid fractions altered in GBA-PD were useful for stratifying idiopathic PD patients. Idiopathic PD patients in the top quartile of GlcCer/SM ratios at baseline showed a more rapid decline in Montreal Cognitive Assessment scores during longitudinal follow-up compared to those in the lowest quartile with a P-value of 0.036. The GlcCer/SM ratio was negatively associated with α-synuclein levels in CSF of PD patients. This study highlights glucosylceramide as a pathway biomarker for GBA-PD patients and the GlcCer/SM ratio as a potential stratification tool for clinical trials of idiopathic PD patients. Our sphingolipids data together with the clinical, imaging, omics, and genetic characterization of PPMI will contribute a useful resource for multi-modal biomarkers development.
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Registered trials
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