Session Information
Date: Tuesday, September 24, 2019
Session Title: Parkinsonisms and Parkinson-Plus
Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: To estimate activity of lysosomal enzymes and lysosphingolipids concentration in dry blood spot of patients with synuleinopathies: Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA).
Background: Synucleinopathies are group of neurodegenerative diseases characterized by the abnormal accumulation of alpha-synuclein aggregates which leads to neuronal death. Mutations in the gene (GBA) encoding for lysosomal enzyme glucocerebrosidase proofed to be high risk for PD and DLB. In recent years, the contribution of other genes that encode lysosomal enzymes to the pathogenesis of synucleinopathies has been discovered.
Method: Our study included 111 PD patients, 13 MSA patients, 11 DLB patients, and 108 controls. Lysosphingolipids (hexosylsphingosine HexSph (glucosylsphingosine (GlcSph)+ galactosylsphingosine (GalSph)), LysoGB3, LysoSM, Lyso509) levels and activity of lysosomal enzymes (Glucocerebrosidase (GCase), Galactosylceramidase (GALC), Alpha-galactosidase (GLA), Alpha-L-iduronidase (IDUA), Acid sphingomyelinase (ASM)) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in dry blood spots.
Results: The concentration of HexSph (GalSph + GlcSph) was significantly increased in MSA patients compared with all the studied groups (P<0.0001). At the same time, an increase of HexSph concentration was detected in LBD patients compared to PD patients (P=0.045) but not compared to control group (P=0.13). Also, in patients with MSA we found an increase in LysoSM concentration as compared to patients with LBD (P=0.033) and control group (P=0.017). Moreover, Lyso509 was increased in MSA patients compared to LBD patients (P=0,037) and controls (P=0,042). We found no significant changes in enzymatic activities between the groups.
Conclusion: Here, we demonstrated increased HexSph, LysoSM and Lyso509 concentrations in blood of patients with MSA. In the LBD group, HexSph level was elevated, but not as pronounced as in patients with MSA, the most aggressive synucleinopathy. At the same time, no differences between PD and controls were revealed. The obtained results allow us to extend our knowledge about the pathogenesis of synucleinopathies.
To cite this abstract in AMA style:
K. Senkevich, G. Baydakova, A. Emelyanov, M. Nikolaev, A. Kopytova, I. Miliukhina, E. Gracheva, A. Kudrevatykh, I. Krasakov, L. Khublarova, I. Fursova, Y. Irishina, N. Zalutskaya, Y. Beltseva, E. Zakharova, S. Pchelina. Increased lysosphingolipids levels in blood of patients with multiple system atrophy [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/increased-lysosphingolipids-levels-in-blood-of-patients-with-multiple-system-atrophy/. Accessed June 15, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-lysosphingolipids-levels-in-blood-of-patients-with-multiple-system-atrophy/