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/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.