Objective: To test the association between plasma lipids and Parkinson disease (PD) diagnosis.

Background: PD is a common neurodegenerative disease whose pathological hallmark is the accumulation of intracellular α-synuclein aggregates in Lewy bodies. Lipid metabolism dysregulation may play a significant role in PD pathogenesis; however, large plasma lipidomics studies in PD are lacking.

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 significant 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: Our results suggest that higher plasma GM3 levels are associated with PD diagnosis. GM3 lies in the same glycosphingolipid metabolic pathway as GlcCer, a substrate of the enzyme glucocerebrosidase, which has been associated with PD. These findings are consistent with previous reports implicating lower glucocerebrosidase activity with PD risk.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/elevated-gm3-plasma-concentration-in-idiopathic-parkinsons-disease-a-lipidomics-analysis/