2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 55(2021) N 2 p. 299-305; DOI 10.1134/S002689332101009X Full Text

D.G. Kulabukhova1,2, L.A. Garaeva1,3, A.K. Emelyanov1,2, K.A. Senkevich1,2, E.V. Gracheva4, I.V. Miliukhina1,2,4, E.Y. Varfolomeeva1,3, A.A. Timofeeva2, A.L. Schwartsman1, T.A. Shtam1,3, S.N. Pchelina1,2,3,4*

Plasma Exosomes in Inherited Forms of Parkinson's Disease

1Konstantinov Petersburg Nuclear Physics Institute, National Research Center Kurchatov Institute, Gatchina, 188300 Russia
2First Pavlov State Medical University of St. Petersburg, St. Petersburg, 197022 Russia
3National Research Center "Kurchatov Institute," Moscow, 123182 Russia
4Institute of Experimental Medicine, St. Petersburg, 197376 Russia

Received - 2020-08-07; Revised - 2020-08-07; Accepted - 2020-08-10

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.

Parkinson's disease, alpha-synuclein, exosomes, LRRK2, GBA