Comparative Transcriptome Analysis in Monocyte-Derived Macrophages of Asymptomatic Mutation Carriers and Patients with GBA-Associated Parkinson's Disease.

Mutations of the gene, encoding for lysosomal enzyme glucocerebrosidase (GCase), are the greatest genetic risk factor for Parkinson's disease (PD) with frequency between 5% and 20% across the world. N370S and L444P are the two most common mutations in the gene. PD carriers of severe mutation L444P in the gene is characterized by the earlier age at onset compared to N370S. Not every carrier of mutations develop PD during one's lifetime. In the current study we aimed to find common gene expression signatures in PD associated with mutation in the gene (GBA-PD) using RNA-seq. We compared transcriptome of monocyte-derived macrophages of 5 patients with GBA-PD (4 L444P/N, 1 N370S/N) and 4 asymptomatic mutation carriers (GBA-carriers) (3 L444P/N, 1 N370S/N) and 4 controls. We also conducted comparative transcriptome analysis for L444P/N only GBA-PD patients and GBA-carriers. Revealed deregulated genes in GBA-PD independently of mutations (L444P or N370S) were involved in immune response, neuronal function. We found upregulated pathway associated with zinc metabolism in L444P/N GBA-PD patients. The potential important role of in the pathogenesis of GBA-PD was suggested.