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Lookup NU author(s): Professor Tiago OuteiroORCiD
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© 2017 Elsevier Ltd Introduction Mutations in the GBA gene, encoding for the lysosomal enzyme glucocerebrosidase, are associated with Gaucher disease. Alterations in plasma sphingolipids have been reported in Gaucher, and similarly in brain extracts in Lewy body disease. As GBA mutations are prevalent risk factors for Parkinson's disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson's patients with and without GBA mutations. Methods We sequenced all GBA exons in 415 Parkinson's patients, previously genotyped for LRRK2. 64 patients (29 GBA positive vs. 35 non-GBA-carriers including 18 LRRK2 positive and 17 non-mutated) were analyzed for chitotriosidase activity and for the concentration of 40 lipid classes using HPLC-MS. Results 29/415 patients (6.9%) carried 8 different GBA mutations associated with Gaucher or Parkinson's, including one novel mutation. Chitotriosidase activity was similar across the genetic groups, while the levels of key lipids were altered in GBA mutation carriers: Monohexosylceramide, Ceramide and Sphingomyelin were elevated; while Phosphatidic acid (PA), Phosphatidylethanolamine (PE), Plasmalogen phosphatidylethanolamine (PEp) and Acyl Phosphatidylglycerol (AcylPG) were decreased. Conclusion The results suggest an important role for these lipids in GBA mediated Parkinson's disease and assist in the identification of common pathways between Gaucher and Parkinson's. Ultimately, our findings may lead to the identification of novel biomarkers for individuals at increased risk of developing Parkinson's disease.
Author(s): Guedes LC, Chan RB, Gomes MA, Conceição VA, Machado RB, Soares T, Xu Y, Gaspar P, Carriço JA, Alcalay RN, Ferreira JJ, Outeiro TF, Miltenberger-Miltenyi G
Publication type: Article
Publication status: Published
Journal: Parkinsonism and Related Disorders
Print publication date: 01/11/2017
Online publication date: 01/09/2017
Acceptance date: 27/08/2017
ISSN (print): 1353-8020
ISSN (electronic): 1873-5126
Publisher: Elsevier Ltd
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