Objective: To evaluate peripheral biochemical markers as well as clinical features of GBA-related Parkinson’s Disease (GBA-PD) subjects over a 2-year follow-up in comparison with NM-PD subjects.

Background: GBA-PD subjects bear a more severe clinical phenotype and are at increased risk of faster disease progression than the non-mutated PD (NM-PD).

Method: Forty-three subjects (17 GBA-PD, 13 NM-PD, 13 HC) completed the 2-year assessment. In these subjects we evaluated alpha-synuclein levels, GCase enzymatic activity and main GCase-related lysosomal proteins in peripheral blood mononuclear (PBMCs) cells as well as motor and non-motor features.

Results: The levels of alpha-synuclein and the GCase activity did not change over time within each group. However, in the GBA-PD we detected significantly higher levels of α-synuclein and lower GCase activity as compared to the NM-PD group both at baseline and at follow-up. Interestingly, in the GBA-PD patients alpha synuclein levels and GCase activity depended on mutation severity, thus identifying a distinctive biochemical profile. GBA-PD subjects showed a more severe motor progression with a higher disease severity compared to NM-PD

Conclusion: This longitudinal study highlights for the first time the role of the PBMCs alpha-synuclein as a valuable parameter to distinguish the GBA-PD condition from NM-PD over time. Our findings confirm the faster progression of disease in the GBA-PD subjects toward a malignant outcome and underscore the need to identify specific biomarkers for the early detection of the condition. This step is extremely important for the prognosis, but also for the development of targeted early interventions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evolution-of-biochemical-and-clinical-signature-of-gba-related-parkinsons-disease-a-2-year-longitudinal-study/