High Performance Liquid Chromatography-Mass Spectrometry (LC-MS) Based Quantitative Lipidomics Study of Ganglioside-NANA-3 Plasma to Establish Its Association with Parkinson's Disease Patients.

BACKGROUND It is well known that, pathologically, Parkinson's disease is a common neurodegenerative disorder. In Parkinson's disease, the protein which is abundant in the human brain, alpha-synuclein, accumulates inside the nerve cells. In this situation, dysregulation of lipid metabolism performs a crucial role; however, its association with Parkinson's disease is has not yet been explored. MATERIAL AND METHODS We performed a high-performance liquid chromatography-mass spectrometry-derived quantitative lipidomics study to analyze the profile of lipidomic plasma obtained from 170 PD patients and 120 controls, taken from our hospital. A logistic regression model was used for analysis in each of the lipid species having all major classes of glycerolipids, sterols, sphingolipids, and glycerophospholipids. RESULTS We observed that there are differences in the plasma concentrations of 2 lipid subclasses, triacylglycerides and ganglioside-NANA-3, between control and Parkinson's disease participants. The most significant difference between both the participants was observed in the case of ganglioside-NANA-3 plasma concentration (1.293±0.029 pmol/µl versus 1.488±0.041 pmol/µl, respectively) after normalizing it with respect to total lipid. Further, a group of 22 glucosylceramide and ganglioside-NANA-3 species concentration was used for receiver operating characteristic curve analysis after normalizing it with respect to total lipid. The results were quite consistent with previously reported biomarker results. CONCLUSIONS Our results show that there is quite good association between high concentration of ganglioside-NANA-3 species and Parkinson's disease. Interestingly, the same metabolic pathway of glucosylceramide, which is a substrate of the enzyme glucocerebrosidase, has been linked with Parkinson's disease, which is at last followed by ganglioside-NANA-3. These results are supported by earlier works in which lower glucocerebrosidase activity has led to risk of the disease.