Our manuscript “Shared and distinct lipid profiles in amygdala from sporadic and GBA-associated Parkinson’s Disease” is accepted for publication at npj Parkinson’s Disease (IF: 8.2).
In this work, we found extensive metabolic remodelling of lipids in amygdala from people with sporadic PD and disease duration above 30 years and from people with PD carriers of a GBA risk mutation. Besides increases in the levels of the substrate of Glucocerebrosidase (GCase), the protein encoded by the gene GBA, i.e. glucosylceramide, and sphingolipids, we observed increased free cholesterol, diacylglyceride and most glycerophospholipids in these samples relative to healthy controls. Moreover, we found a shift from short to long sphingomyelin and ceramide and from long to short phosphatidylserine and phosphatidylethanolamine in sPD (>30y) and PD-GBA risk cases, and the opposite in PD-GBA severe cases. The levels of lipid classes and the relative proportion of lipid species affected in PD amygdala all correlated with GCase activity and/or pathological alpha-synuclein levels.
We believe that the distinct lipid phenotypes observed across PD subgroups underscore the importance of patient stratification in clinical trials aiming at reverting PD-related lipid changes.
Congratulations to Sonia Sanz Muñoz and Frederik Ravnkilde Marlet for co-leading this work! Thank you to the other members of our group, Jesper Dreier, Katharina Schott, Krista Stenstrøm Neergaard, and our collaborators, Mesut Bilgin,Erwan Bezard, Benjamin DEHAY, Zane Jaunmuktane and Kenji Maeda for their excellent contribution to this work!
This work was supported by the Novo Nordisk Foundation, Lundbeckfonden / Lundbeck Foundation, Carlsberg Foundation, Parkinsonforeningen, Independent Research Fund Denmark, Innovation Fund Denmark under the framework of EraPermed.
Galvagnion Group 