Elevated GM3 Plasma Concentration in Parkinson’s Disease: a Lipidomics Analysis (P1.006)

Objective: To test the association between plasma lipids and Parkinson disease (PD) diagnosis Background: Lipid metabolism dysregulation may play a significant role in PD pathogenesis; however, large plasma lipidomics studies in PD are lacking Design/Methods: We analyzed the lipidomic profile of plasma obtained from 150 idiopathic PD patients and 100 controls, taken from the ‘Spot’ study at Columbia University Medical Center in New York. Our mass spectrometry based analytical panel consisted of 520 lipid species from 39 lipid sub classes including all major classes of glycerophospholipids, sphingolipids, glycerolipids and sterols. Each lipid species was analyzed using a logistic regression model. Results: The plasma concentration of 9 lipid sub classes was different between PD and control participants. Of these, monosialodihexosylganglioside (GM3) ganglioside concentration had the most robust difference between PD and controls ( 1.531±0.037 pmol/μl versus 1.337±0.040 pmol/μl respectively; p-value = 2.890E-05; q-value = 2.933E-03). Next, we used a collection of 20 GM3 and glucosylceramide (GlcCer) species concentrations to perform a ROC curve analysis, and found that these lipids compare favorably with biomarkers reported in previous studies (AUC = 0.742 for males, AUC = 0.644 for females). Conclusions: Higher plasma GM3 levels are associated with PD diagnosis. In the glycosphingolipid metabolic pathway, GM3 is upstream to the enzyme glucocerebrosidase, which has been associated with PD, but it is not its direct substrate. These findings are consistent with previous reports implicating lower glucocerebrosidase activity with PD risk. Study Supported by: Parkinson’s Disease Foundation, the National Institutes of Health (K02NS080915, and UL1 TR000040, formerly the National Center for Research Resources, Grant Number UL1 RR024156 and P50 AG008702) Disclosure: Dr. Alcalay has received personal compensation for travel and consultation fees from Sanofi Genzyme and Prophase. Dr. Chan has nothing to disclose. Dr. Perotte has nothing to disclose. Dr. Zhou has nothing to disclose. Dr. Liong has nothing to disclose. Dr. Shorr has nothing to disclose. Dr. Marder has received personal compensation in an editorial capacity for Current Neuroscience. Dr. Kang has received research support from Allergan. Dr. Waters has received personal compensation for activities with UCB and Teva as a speaker. Dr. Levy has nothing to disclose. Dr. Xu has nothing to disclose. Dr. Shim has nothing to disclose. Dr. Pe9er has nothing to disclose. Dr. Di Paolo has received personal compensation for activities with Denali Therapeutics as an employee.