| Autor: |
López de Frutos L; Fundación para el Estudio y la Terapéutica de la Enfermedad de Gaucher y Otras Lisosomales (FEETEG), 50006 Zaragoza, Spain.; GIIS-012, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain., Almeida F; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649004 Lisbon, Portugal., Murillo-Saich J; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA., Conceição VA; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649004 Lisbon, Portugal., Guma M; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.; VA Medical Center, San Diego, CA 92093, USA.; Department of Medicine, Autonomous University of Barcelona, 08193 Bellaterra, Spain., Queheberger O; Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA., Giraldo P; Fundación para el Estudio y la Terapéutica de la Enfermedad de Gaucher y Otras Lisosomales (FEETEG), 50006 Zaragoza, Spain., Miltenberger-Miltenyi G; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649004 Lisbon, Portugal.; Laboratório de Genética, Faculdade de Medicina, Universidade de Lisboa, 1649004 Lisbon, Portugal.; Department of Neurology, Ludwig-Maximilians-Universität München, 80539 Munich, Germany.; Genetics Department, Reference Center on Lysosomal Storage Disorders, Hospital Senhora da Oliveira, 4835-044 Guimarães, Portugal. |
| Abstrakt: |
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. |
