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Extended coverage of human serum glycosphingolipidome by 4D-RP-LC TIMS-PASEF unravels association with Parkinson’s disease

Author

Listed:
  • Huong Giang Vo

    (University Medical Center)

  • Gabriel Gonzalez-Escamilla

    (University Medical Center
    Saarland University, Saarland University Hospital)

  • Daniela Mirzac

    (University Medical Center)

  • Lilia Rotaru

    (Diomid Gherman Institute of Neurology and Neurosurgery)

  • Damian Herz

    (University Medical Center)

  • Sergiu Groppa

    (University Medical Center
    Saarland University, Saarland University Hospital)

  • Laura Bindila

    (University Medical Center)

Abstract

Glycosphingolipids (GSLs) are important targets in immune, infectious, lysosomal storage diseases, cancer, and neurodegenerative diseases. Circulatory GSLs profiling in clinical samples is restricted by the lack of mid- and high-throughput analytical methods and deep coverage of long-chain sialylated glycosphingolipidome. We present a 4-dimensional (4D)-glycosphingolipidomics platform for routine glycosphingolipidome profiling encompassing: extraction and fractionation of sialylated GSLs with 3 to 15 monosaccharides, neutral GSLs and sulfatides; µL-flow reversed-phase LC-TIMS-PASEF MS analysis; semi-quantification strategy adapted for fractionated glycosphingolipidome, and referential CCS, RT, and m/z values for GSLs annotation. 4D-glycosphingolipidomics of human serum reveals a high structural heterogeneity, amounting to 376 GSLs: 159 GSLs of ganglio- and neolacto-series, 145 neutral GSLs and 72 sulfatides. Here we demonstrate the platform’s utility for clinical profiling of Parkinson’s disease (PD) sera. 41 neolacto- and ganglio-species discriminate PD patients from controls and 14 GSLs differentiate sex subgroups, laying the foundation for further functional GSL studies with PD.

Suggested Citation

  • Huong Giang Vo & Gabriel Gonzalez-Escamilla & Daniela Mirzac & Lilia Rotaru & Damian Herz & Sergiu Groppa & Laura Bindila, 2025. "Extended coverage of human serum glycosphingolipidome by 4D-RP-LC TIMS-PASEF unravels association with Parkinson’s disease," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59755-6
    DOI: 10.1038/s41467-025-59755-6
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