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Plasma Exosomes in Inherited Forms of Parkinson’s Disease

  • MOLECULAR CELL BIOLOGY
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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Alpha-synuclein misfolding and aggregation resulting in neurototoxicity is a hallmark of PD. The prion properties of alpha-synuclein are still under discussion. Exosomes (extrcellular vesicles 40–100 nm in size) can play a key role in the transport of pathogenic forms of alpha-synuclein. The most frequent inherited forms of the disease are PD associated with mutation in the leucine-rich repeat kinase 2 (LRRK2-PD) and glucocerebrosidase (GBA-PD) genes. The aim of our work is to evaluate the concentration and size of exosomes derived from blood plasma of patients with GBA-PD, asymptomatic GBA mutation carriers, and the effect of GBA and LRRK2 mutations on alpha-synuclein level in exosomes derived from peripheral blood plasma. Plasma extracellular vesicles were isolated via chemical precipitation and sequential ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis (NTA), and flow cytometry. Total alpha-synuclein level in plasma exosomes was estimated by enzyme-linked immunosorbent assay. Patients with sporadic PD, PD with dementia, patients with inherited PD (GBA-PD, LRRK2-PD), and GBA mutation carriers were included in the study. The concentration on plasma exosomes was higher in GBA-PD patients that in sporadic PD patients, asymptomatic carriers of mutations on GBA gene, and control (p = 0.004, 0.019 and 0.0001 respectively). The size of plasma exosomes was higher in GBA-PD patients compared to asymptomatic carriers of GBA mutations and control (p = 0.009 and 0.0001, respectively). No significant difference was found for exosomal alpha-synuclein levels in the studied groups. Our results allowed us to suggest that a decrease in GBA activity may affect the pool of plasma exosomes, and mutations in the LRRK2 and GBA genes do not influence the level of plasma exosomal alpha-synuclein.

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ACKNOWLEDGMENTS

We would like to express our gratitude to A.N. Gorshkov (Smorodintsev Research Institute of Influenza) for conducting experiments with transmission electron microscopy.

Funding

The study was supported by the Russian Foundation for Basic Research (project nos. 18-015-00262A (screening of mutations in genes GBA and LRRK2 and assessing the concentration of alpha-synuclein in blood plasma exosomes; 19-315-90059 Postgraduate students (characterization of extracellular vesicles by flow cytometry, Western blotting) and the Russian Science Foundation no. 19-15-00315 (characterization of vesicles by the NTA method in groups of asymptomatic carriers of mutations GBA, patients with GBA-PD).

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Authors and Affiliations

  1. Konstantinov Petersburg Nuclear Physics Institute, National Research Center Kurchatov Institute, 188300, Gatchina, Russia

    D. G. Kulabukhova, L. A. Garaeva, A. K. Emelyanov, K. A. Senkevich, I. V. Miliukhina, E. Y. Varfolomeeva, A. L. Schwartsman, T. A. Shtam & S. N. Pchelina

  2. First Pavlov State Medical University of St. Petersburg, 197022, St. Petersburg, Russia

    D. G. Kulabukhova, A. K. Emelyanov, K. A. Senkevich, I. V. Miliukhina, A. A. Timofeeva & S. N. Pchelina

  3. National Research Center “Kurchatov Institute”, 123182, Moscow, Russia

    L. A. Garaeva, E. Y. Varfolomeeva, T. A. Shtam & S. N. Pchelina

  4. Institute of Experimental Medicine, 197376, St. Petersburg, Russia

    E. V. Gracheva, I. V. Miliukhina & S. N. Pchelina

Authors
  1. D. G. Kulabukhova
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  2. L. A. Garaeva
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  3. A. K. Emelyanov
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  6. I. V. Miliukhina
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  7. E. Y. Varfolomeeva
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  8. A. A. Timofeeva
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  9. A. L. Schwartsman
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  10. T. A. Shtam
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  11. S. N. Pchelina
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Corresponding author

Correspondence to S. N. Pchelina.

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Conflict of interest. The authors declare they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in this work are in accordance with the ethical standards of the institutional committee on research ethics and the Declaration of Helsinki 1964 and its subsequent amendments or comparable standards of ethics. Informed consent was obtained from all patients.

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Abbreviations: PD, Parkinson’s disease; CSF, cerebrospinal fluid; LRRK2, leucine repeat enriched kinase 2; GBA, glucocerebrosidase; PDD, PD with dementia; GBA-PD, PD associated with mutations in the GBA gene; LRRK2-PD, PD associated with mutations in the with mutations in the LRRK2 gene; sPD, sporadic PD; AC-GBA, asymptomatic carriers of mutations in the GBA gene; SU, sequential ultracentrifugation; CP, chemical precipitation; NTA, nanoparticle trajectory analysis; TEM, Transmission Electron Microscopy.

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Kulabukhova, D.G., Garaeva, L.A., Emelyanov, A.K. et al. Plasma Exosomes in Inherited Forms of Parkinson’s Disease. Mol Biol 55, 297–303 (2021). https://doi.org/10.1134/S002689332101009X

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