Alcalay RN

Carriço JA

Chan RB

Conceição VA

Ferreira JJ

Gaspar P

Gomes MA

Guedes LC

Machado RB

Miltenberger-Miltenyi G

Outeiro TF

Soares T

Xu Y

\ua9 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\u27s disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson\u27s patients with and without GBA mutations. Methods We sequenced all GBA exons in 415 Parkinson\u27s 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\u27s, 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\u27s disease and assist in the identification of common pathways between Gaucher and Parkinson\u27s. Ultimately, our findings may lead to the identification of novel biomarkers for individuals at increased risk of developing Parkinson\u27s disease

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Serum lipid alterations in <em>GBA</em>-associated Parkinson\u27s disease

Serum lipid alterations in <em>GBA</em>-associated Parkinson\u27s disease

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