biostudies-otherUnknownDeutsche ForschungsgemeinschaftHomo sapiens (human)https://www.ebi.ac.uk/biostudies/studies/S-BSST1880biostudies-other10.1002/mds.28186CRC1039 A03CRC1039 Z01falsePlasma lipidomic signatures in patients with idiopathic Parkinson's DiseaseThe pathology of Parkinson's Disease (PD) arises from a deposition of oligomeric forms of alpha-synuclein (gene: SNCA, alphaSyn). Glycosphingolipids facilitate the formation of such oligomers and interfere with their lysosomal degradation. In previous studies we (DOI: 10.1002/mds.28186) and others (DOI: 10.1093/brain/awac176) have observed increased plasma concentrations of ceramides and glucosylceramides or glucosylsphingosines in plasma of patients with idiopathic PD who were not carrying GBA1 mutations that are associated with mal-folding or dysfunction of the GBA1 gene product, lysosomal glucocerebrosidase alpha (GCase). To gain further insight into PD-associated ceramide pathology we explored and compared lipidomic patterns in plasma using UHPLC-MS/MS lipidomic analyses. Plasma lipidomic studies of 50 PD patients versus 50 age matched healthy controls (HC) revealed increased hexosylceramides in PD, particularly GlcCer24:1, stronger in male than female PD patients, whereas a number of mono- and poly-unsaturated fatty acids were reduced without differences between sexes. In addition, phosphatidylcholine species (PC) shifted from long chain poly-unsaturated PC species to shorter mono-unsaturated PCs without overall change of summed PCs. PCs are connected with GlcCer via the phospholipid translocase ATP10 (ATP10A, 10B and 10D), which flips PC in exchange with GlcCer in the plasma membrane, and contributes thereby to membrane dynamics, and is considered as PD risk gene. The results confirm the pathology of glucosylated sphingolipids in PD and provide further insight into PD-associated lipidomic patterns. Patient recruitment and UHPL-MS/MS analyses PD patients, diagnosed using ICD10 diagnostic criteria for Parkinson's Disease and age-matched healthy control subjects were consecutively recruited. PD disease severity was assessed according to the Hoehn Yahr rating scale. Informed written consent was obtained from all subjects. Blood was collected in 9 ml K3+ EDTA tubes, centrifuged at 1300 g and plasma was transferred into 1.5 ml tubes and stored at -80°C until further use. Lipidomic analysis were conducted essentially as described (DOI: 10.1152/ajpcell.00630.2024). A methyl-tert-butyl-ether (MTBE) and methanol-based liquid-liquid extraction was used for lipid extraction and lipidomic analysis. For chromatographic separation of lipids, a Zorbax RRHD Eclipse Plus C8 1.8 µm 50 x 2.1 mm ID column (Agilent, Waldbronn, Germany) with a pre-column of the same type was used. The mobile phases were (A) 0.1% formic acid and 10 mM ammonium formate and (B) 0.1% formic acid in acetonitrile:isopropanol (2:3, v/v). Analysis of lipids in human plasma samples was performed on a Nexera X2-UHPLC system (Shimadzu Corporation, Kyoto, Japan) coupled to a Sciex TripleTOF 6600 operated by Analyst®TF Software (RRID:SCR_015785) v1.7.1 (both Sciex, Darmstadt, Germany). The TOF-MS1 scan covered a mass range of 100-1000 m/z at 30,000 mass resolution and six data dependent MS/MS spectra in mass range of 50-1000 m/z in high sensitivity mode. Relative quantification was performed in MultiQuant 3.02 software and peak identification in MasterView v1.1 software (both Sciex, Darmstadt, Germany). The area under the curve (AUC) was used for quantification. AUC were transformed to square root of the AUCs (sqrt AUC) for data analysis. 2025-08-23T00:00:00Z2025-08-16T16:45:22.5Z2025-02-22T16:39:24.947ZS-BSST1880S-BSST38910.1002/mds.28186