Category: Parkinson's Disease: Genetics
Objective: This study aims to characterize blood profile of alpha-synuclein and the main lysosomal proteinsas well as clinical features of PD subjects carrying GBA1 mutations (GBA-PD) and compared them to sporadic PD (iPD).
Background: Mutations in the GBA1 gene, encoding the lysosomal enzyme glucocerebrosidase (GCase), are the most frequent risk factor for Parkinson’s disease (PD).
Method: In this study we recruited 14 GBA-PD, 25 PD subjects without GBA1 mutations (iPD) and 31 healthy subjects (HC). We evaluated alpha-synuclein levels in peripheral blood lymphocytes, plasma exosomes and whole plasma and lysosomal alterations in lymphocytes by analyzing the expression of the main GCase-related proteins (cathepsin D, LAMP1, LIMP2, Saposin C). Moreover, we assessed motor and non-motor signs in all subjects by means of clinical questionnaires and scales (MoCA, UPSIT, RBDsq, UPDRS-III, SCOPA-AUT and BDI).
Results: GCase activity was significantly affected in PD-GBA patients compared with iPD and HC. In GBA-PD, decreased GCase activity was associated with higher alpha-synuclein levels in lymphocytes compared with iPD. Both GBA-PD and iPD patients showed increased levels of exosomal alpha-synuclein; whereas plasma exosomal α-syn/total α-syn ratio was significantly higher in iPD than in GBA-PD. Interestingly, a significant inverse correlation between GCase activity and plasma exosomal α-syn/total α-syn ratio was detected, suggesting a potential mechanism by which changes in GCase activity may affect the α-synuclein release.The GBA-PD group also displayed lower Saposin C levels and higher LIMP-2 levels compared to iPD. A prevalence of non-motor features were also observed in GBA-PD group compared to iPD.
Conclusion: This study confirms the presence of distinctive lysosomal alterations related to GCase enzyme deficiency in GBA-PD group compared to iPD and highlights that differences also exist in the blood alpha-synuclein profile between patient’s group. These features could be distinctive of GBA-related condition and potentially trigger pathological conversion.
To cite this abstract in AMA style:
M.A Avenali, S.C Cerri, G.O Ongari, C.P Pacchetti, C.T Tassorelli, E.V Valente, F.B Blandini. Blood alpha-synuclein profile and lysosomal alterations distinguish GBA1-related Parkinson’s disease from sporadic Parkinson’s disease [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/blood-alpha-synuclein-profile-and-lysosomal-alterations-distinguish-gba1-related-parkinsons-disease-from-sporadic-parkinsons-disease/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/blood-alpha-synuclein-profile-and-lysosomal-alterations-distinguish-gba1-related-parkinsons-disease-from-sporadic-parkinsons-disease/