Objective: To better understand lysosomal dysfunction in Parkinson’s Disease.
Background: Lysosomal dysfunction and α-synuclein accumulation play central roles in Parkinson’s Disease. They are interconnected by a self-reinforcing loop. In GBA1-PD, lowered activity of the GBA1-encoded lysosomal enzyme glucosylceramidase seems to be the primary driver. In idiopathic PD, a primary driver remains to be defined. Identification of abnormal metabolite levels in PD patients may facilitate pertinent insights.
Method: Using mass-spectrometry, we measured a battery of lysosome-related metabolites in dried blood spot filtercards from PD patients (N=3,335) and controls that had been matched for gender, age and sample age (N=3,146). The patients had been enrolled in the frame of ROstock PArkinson’s Disease (ROPAD), an observational clinical study that primarily aimed at comprehensively defining the genetic basis of PD. Both, patients with GBA1-PD (N=840) and with idiopathic PD (N=2,495) were included. Also the controls either had heterozygous PD-relevant GBA1 variants (N=666) or were GBA1 wildtype (N=2,480).
Results: Consistent with previous studies, total glucosylceramides were significantly elevated in PD patients over controls (1.09-fold; p<1.0 x 10-10) independent of GBA1 genetic status. PD patients also had significantly higher levels of the sphingolipid Lyso-Gb3 (1.06-fold; p<1.0 x 10-10), and also this difference was independent from GBA1 genetic status. Interestingly, Lyso-Gb3 is a well-established biomarker for Fabry Disease (FD), an X-linked lysosomal storage disorder.
Conclusion: Our findings provide new insights into the ongoing discussion regarding a potential genetic link between FD and PD. More broadly, they establish a novel foundation for understanding the role of lysosomal dysfunction in PD. Further research is required to determine whether increased Lyso-Gb3 is a contributing cause or a consequence of the disease.
To cite this abstract in AMA style:
C. Beetz, C. Cozma, M. Iurascu, S. Fischer, S. Oppermann, K. Kandaswamy, P. Bauer. The sphingolipid Lyso-Gb3, a biomarker for the lysosomal storage disorder Fabry Disease, is significantly elevated in blood from patients with Parkinson’s Disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/the-sphingolipid-lyso-gb3-a-biomarker-for-the-lysosomal-storage-disorder-fabry-disease-is-significantly-elevated-in-blood-from-patients-with-parkinsons-disease/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-sphingolipid-lyso-gb3-a-biomarker-for-the-lysosomal-storage-disorder-fabry-disease-is-significantly-elevated-in-blood-from-patients-with-parkinsons-disease/