Objective: The aim of this proejct is to identify novel biomarkers of Parkinson’s disease diagnosis and progression, with a focus on GBA-PD.

Background: Our previous research identified notable differences in platelet alpha-synuclein levels among glucocerebrosidase (GBA1) mutation carriers with Parkinson’s disease (PD), potentially implicating alpha-synuclein as both a contributor to PD pathogenesis and a biomarker for disease conversion. However, the connection between altered alpha-synuclein and impaired GBA1 enzyme function remains unclear, particularly regarding lipid metabolism and associated lipidomic changes.

Method: To investigate this relationship, we recruited and established a comprehensive cohort comprising five distinct health statuses: GBA1 mutation carriers without PD; idiopathic PD (iPD); GBA mutation carriers with PD (GBA-PD); Gaucher disease (GD) patients without PD; and healthy controls. Using targeted and untargeted lipidomics, we quantified GBA1 enzyme substrates and conducted a comprehensive lipidomic profiling, respectively.

Results: Standard descriptive analyses revealed significant elevations of known GBA1 substrates, glucosylceramide and glucosylsphingosine, in groups diagnosed with GBA-PD, iPD, and, as anticipated, GD patients. To further explore these observations, principal component analysis (PCA) was employed, followed by linear discriminant analysis (LDA) on the complete lipidomic dataset. The multivariate analyses demonstrated distinct lipidomic signatures, clearly differentiating among the study groups.

Detailed examination of the LDA components highlighted specific disruptions in phospholipid metabolism uniquely associated with GBA1 mutant groups, whereas individuals with idiopathic PD displayed significant alterations primarily in sphingomyelin metabolism.

Conclusion: These findings underscore the potential utility of platelet lipidomics as an accessible biochemical parameter, facilitating the identification of specific lipid biomarkers suitable for large-scale screening and potentially informing the development of novel blood-based diagnostic tools for PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/platelets-lipidome-as-potential-biomarker-of-parkinsons-disease/