75ea44a093c76ca199c971dcabd8af45 292225.pdf d134d6c65151c77aa20e9e1b8cb6553914040b32 292225.pdf 6eff0c931aeab788e33b296617011892a8285b1eeffd7d94edd7aafb7b5ec0a6 292225.pdf Title: Serum Phospholipid Profile Changes in Gaucher Disease and Parkinson’s Disease Subject: Alterations in the levels of serum sphingolipids and phospholipids have been reported in Gaucher disease and in Parkinson’s disease, suggesting a potential role of these lipids as biomarkers. This project’s objective is to detect novel associations and novel candidate biomarkers in the largest Spanish Gaucher and Parkinson diseases of the Iberian Peninsula. For that, 278 participants were included: 100 sporadic Parkinson’s patients, 70 Gaucher patients, 15 GBA1-mutation-carrier Parkinson’s patients and 93 controls. A serum lipidomics array including 10 phospholipid groups, 368 species, was performed using high-performance liquid chromatography–mass spectrometry. Lipid levels were compared between groups via multiple-regression analyses controlling for clinical and demographic parameters. Additionally, lipid levels were compared within the Gaucher and Parkinson’s groups controlling for medication and/or disease severity. Results were controlled for robustness by filtering of non-detectable lipid values. There was an increase in the levels of phosphatidylcholine, with a simultaneous decrease in lyso-phosphatidylcholine, in the Gaucher, Parkinson’s and GBA1-mutation-carrier Parkinson’s patients vs. controls. Phosphatidylethanolamine, lyso- and plasmalogen-phosphatidylethanolamine were also increased in Gaucher and Parkinson’s. Gaucher patients also showed an increase in lyso-phosphatidylserine and phosphatidylglycerol. While in the Gaucher and Parkinson’s groups, velaglucerase alpha and dopamine agonists, respectively, showed positive associations with the lipid changes, miglustat treatment in Gaucher patients normalized the altered phosphatidylcholine/lyso-phosphatidylcholine ratio. In conclusion, Gaucher and Parkinson’s patients showed changes in various serum phospholipid levels when compared with healthy controls, further supporting the role of such lipids in disease development and, possibly, as putative biomarkers. This hypothesis was reinforced by the normalizing effect of miglustat, and by controlling for data robustness, even though the limited number of participants, especially in the sub-distribution by treatment groups in GD requires validation in a larger number of patients. Keywords: Parkinson’s disease; Gaucher disease; plasma phospholipids; GBA1; miglustat; dopamine agonist Author: Laura López de Frutos, Francisco Almeida, Jessica Murillo-Saich, Vasco A. Conceição, Monica Guma, Oswald Queheberger, Pilar Giraldo and Gabriel Miltenberger-Miltenyi Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Sep 22 09:05:06 2022 CEST ModDate: Thu Sep 22 09:14:07 2022 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1211368 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- PBJDFE+VnURWPalladioL Type 1 Custom yes yes no 10 0 LBZNLX+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 UNYFNE+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 QSOFZU+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 SENKHV+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 46 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 74 0 AZDANO+CMBSY10 Type 1 Builtin yes yes no 78 0 GQWIGS+CMSY10 Type 1 Builtin yes yes no 82 0 NMEKAF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 96 0 NMEKAH+PalatinoLinotype TrueType WinAnsi yes yes no 99 0 NMEKAJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 102 0 CKBPVA+EURM10 Type 1 Builtin yes yes no 116 0 NMEKAF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 133 0 NMEKAG+PalatinoLinotype CID TrueType Identity-H yes yes yes 136 0 NMEKAH+PalatinoLinotype TrueType WinAnsi yes yes no 142 0 NMEKAJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 145 0 GEJNTL+VnURWPalladioL-Italic Type 1 Custom yes yes no 156 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-25 02:37:11 CEST RepresentationInformation: 292225.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-05-24 13:02:55 CEST Size: 1211368 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 347 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Clinical and Demographic Data Destination: subsection.2.1 Item: Title: Comparison of Absolute Lipid Levels Destination: subsection.2.2 Item: Title: Multiple Regression Analyses Destination: subsection.2.3 Item: Title: Associations between Disease Severity, Medication and the Lipid Levels Destination: subsection.2.4 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Patients Destination: subsection.4.1 Item: Title: Quantification of the Levels of Lipid Groups and Their Species Destination: subsection.4.2 Item: Title: Statistics Destination: subsection.4.3 Children: Item: Title: Comparison of Clinical Data and Absolute Lipid Levels Destination: subsubsection.4.3.1 Item: Title: Between-Group Analyses of Lipid Levels Destination: subsubsection.4.3.2 Item: Title: Within-Group Analyses of Lipid Levels Destination: subsubsection.4.3.3 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Serum Phospholipid Profile Changes in Gaucher Disease and Parkinson’s Disease Author: Laura López de Frutos, Francisco Almeida, Jessica Murillo-Saich, Vasco A. Conceição, Monica Guma, Oswald Queheberger, Pilar Giraldo and Gabriel Miltenberger-Miltenyi Subject: Alterations in the levels of serum sphingolipids and phospholipids have been reported in Gaucher disease and in Parkinson’s disease, suggesting a potential role of these lipids as biomarkers. This project’s objective is to detect novel associations and novel candidate biomarkers in the largest Spanish Gaucher and Parkinson diseases of the Iberian Peninsula. For that, 278 participants were included: 100 sporadic Parkinson’s patients, 70 Gaucher patients, 15 GBA1-mutation-carrier Parkinson’s patients and 93 controls. A serum lipidomics array including 10 phospholipid groups, 368 species, was performed using high-performance liquid chromatography mass spectrometry. Lipid levels were compared between groups via multiple-regression analyses controlling for clinical and demographic parameters. Additionally, lipid levels were compared within the Gaucher and Parkinson’s groups controlling for medication and/or disease severity. Results were controlled for robustness by filtering of non-detectable lipid values. There was an increase in the levels of phosphatidylcholine, with a simultaneous decrease in lyso-phosphatidylcholine, in the Gaucher, Parkinson’s and GBA1-mutation-carrier Parkinson’s patients vs. controls. Phosphatidylethanolamine, lyso- and plasmalogen-phosphatidylethanolamine were also increased in Gaucher and Parkinson’s. Gaucher patients also showed an increase in lyso-phosphatidylserine and phosphatidylglycerol. While in the Gaucher and Parkinson’s groups, velaglucerase alpha and dopamine agonists, respectively, showed positive associations with the lipid changes, miglustat treatment in Gaucher patients normalized the altered phosphatidylcholine/lyso-phosphatidylcholine ratio. In conclusion, Gaucher and Parkinson’s patients showed changes in various serum phospholipid levels when compared with healthy controls, further supporting the role of such lipids in disease development and, possibly, as putative biomarkers. This hypothesis was reinforced by the normalizing effect of miglustat, and by controlling for data robustness, even though the limited number of participants, especially in the sub-distribution by treatment groups in GD requires validation in a larger number of patients. 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