In this study, we discovered the shared lipid signature associated with long sporadic Parkinson’s disease (PD) (sPD), GBA risk and mild mutations, that is distinct from that of GBA severe mutation in PD amygdala.
Moreover, we found that the levels of pathological alpha-synuclein, glucocerebrosidase activity and specific lipids, inc. cholesterol, sphingolipids, cardiolipin and diacylglycerides, correlate in sPD samples. These results provide the first evidence that GBA risk/mild mutations, on one hand, and GBA severe mutation, on the other hand, lead to opposite changes in the lipidome of PD amygdala. Finally, we provide the lipid composition of Lewy Bodies (LBs) and small aggregates (SAs) enriched fractions from PD and PD-GBA amygdala homogenates and found that sPD and GBA risk mutations led to similar lipid changes in LBs and SAs than those observed in homogenates, but to a lesser extent.
These results suggest the need for patient stratification in clinical trials, especially for those testing substrate alternating approaches aiming at reverting PD-related lipid changes.
Galvagnion Group 