Objective: To identify the protein changes and to search the potential biomarkers of PD among GBA mutation carriers.
Background: Mutations in the GBA gene encoding glucocerebrosidase enzyme are the greatest risk factor for one of the most common neurodegenerative disorders, Parkinson’s disease (PD). Molecular mechanisms of PD are unknown. Last data shown the potential role of exosomes in the pathological process of neurodegenerative disorders due to dysfunction of their intercellular communication and encapsulated protein functions [1].
Method: 10 GBA-PD patients, 10 sPD patients, 10 asymptomatic GBA mutations carriers (GBA-carriers) and 10 controls were enrolled. Plasma exosomes from each individual were isolated by via sequential ultracentrifugation. The exosome proteins were analyzed by mass spectrometry. Raw data were analyzed using MaxQuant with label-free quantitative proteomic analysis as presented in [2]. Differential proteomic analysis was conducted by library DEP (v.1.17.1) in R (3.6.2) and LFQ-Analyst with Bayesian principal component analysis as imputation method for missing values (Fold change>1.5,padjusted<0.05) [3,4].
Results: A total of 162 proteins were identified. 82 proteins differ significantly between samples. The expression level of 1 protein was increased in GBA-PD patients compared to controls. The expression level of 4 proteins were significantly increased and 2 decreased in GBA-PD patients than in GBA-carriers. The expression levels of 5 proteins were increased and 11 decreased in GBA-PD patients compared to PD patients. The expression level of 38 proteins were significantly increased and 18 decreased in PD patients than in controls and 22 proteins were decreased and 46 increased in PD patients compared to GBA-carriers. No differences between GBA-carriers and controls were determined. The most significant enrichment pathways for differentially expressed proteins identified using GO database were associated with inflammation, oxidative stress, lipid metabolism, synapse organization.
Conclusion: Using Venn diagram common features of plasma exosome protein profile for GBA-PD and PD were found. Also, we propose some of identified proteins as SPDR, TNL1, CLIC1 might be related to the pathophysiological mechanism of GBA-PD and could be considered as potential biomarkers for PD diagnosis among GBA mutations carriers. The study was supported by RSF grant N19-15-00315.
References: 1. Liu, Wanying et al. “Role of Exosomes in Central Nervous System Diseases.” Frontiers in molecular neuroscience vol. 12 240. 4 Oct. 2019, doi:10.3389/fnmol.2019.00240
2. Ni, H., Pan, W., Jin, Q. et al. Label-free proteomic analysis of serum exosomes from paroxysmal atrial fibrillation patients. Clin Proteom 18, 1 (2021). https://doi.org/10.1186/s12014-020-09304-8
3. Shah, A. D., Goode, R. J. A., Huang, C., Powell, D. R., & Schittenhelm, R. B. (2020). Lfq-Analyst: An easy-To-use interactive web platform to analyze and visualize label-free proteomics data preprocessed with maxquant. Journal of Proteome Research, 19(1), 204-211. https://doi.org/10.1021/acs.jproteome.9b00496
4. Jin, L., Bi, Y., Hu, C. et al. A comparative study of evaluating missing value imputation methods in label-free proteomics. Sci Rep 11, 1760 (2021). https://doi.org/10.1038/s41598-021-81279-4
To cite this abstract in AMA style:
T. Usenko, A. Bezrukova, K. Basharova, D. Kulabukhova, I. Miliukhina, E. Zakharova, S. Naryzhny, S. Pchelina. Differential proteomic analysis of plasma exosomes in Parkinson disease associated with mutations in the GBA gene [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/differential-proteomic-analysis-of-plasma-exosomes-in-parkinson-disease-associated-with-mutations-in-the-gba-gene/. Accessed November 23, 2024.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/differential-proteomic-analysis-of-plasma-exosomes-in-parkinson-disease-associated-with-mutations-in-the-gba-gene/