Category: Parkinson's Disease: Pathophysiology
Objective: To study the role monocytic A-syn and lipids as biomarkers of PD.
Background: A chronic pro-inflammatory pattern is present in Parkinson’s disease (PD) patients’ brain and in peripheral blood, with evidence for a crosstalk between central nervous system and peripheral immune cells. Monocytes display elevated alpha-synuclein (A-syn) levels intracellularly. GBA1 mutations, the major genetic risk factor for PD, also modify GCase expression in phagocytic cells.
Method: We recruited a cohort of patients: GBA carriers without PD (GBA-NMC), idiopathic PD (iPD), GBA carriers with PD (GBA-PD) and healthy controls (HC). Monocytes from 241 patients were screened by ELISA and 4-MUG assay to quantify A-syn levels and GCase activity. We also performed untargeted lipidomic by mass spectrometry in 100 monocytes (25 each group).
Results: Preliminary univariate analysis did not reveal significant changes between groups for A-syn levels and GCase activity. When analysing presence of PD (iPD + GBA-PD), logistic regression analysis revealed a significant association between levels of A-syn and PD (p=0.025). Subsequent multivariate logistic regression analysis showed a significant association between PD diagnosis and A-syn (P=0.022; AUC=0.69). Regarding lipidomics, a significant increase was found in GluCeramide (GluCer) 16:0 and 22:0 in GBA-PD compared to HC. GluCer 24:1 was increased in iPD only. Concerning GCase substrates, a only positive trend was present in GBA-PD and iPD. Comparison between GBA-PD and GBA-NMC showed a significant increase in GBA-PD of 3 substrates: GluCer 16:0, 20:0, and 22:0. GBA-PD presented a significant increase in Glusphingosine (GluSph) compared to HC. Grouping lipids according to genotype did not identify differences. A regression analysis showed a significant association between GluCer 20:0 and GluSph in GBA-PD vs GBA-NMC (p=0.044 and p=0.015, respectively), with an AUC=0.81 for GluCer 20:0 and 0.84 for GluSph.
Conclusion: The lipidomic analysis identified differences between GBA-PD and HC, and also major differences in various GCase substrates and GluSph between GBA-PD and GBA-NMC. No differences were found in substrates in PD groups, which is in line with GCase activity results obtained. This preliminary results indicate GluCer 20:0 and GluSph levels could represent a potential PD biomarker in GBA carriers. A-syn and selected GluCer species in monocytes could be exploited as potential marker for PD.
To cite this abstract in AMA style:
S. Lucas-Del-Pozo, G. Uras, D. Moreno-Martinez, F. Fierli, S. Koletsi, C. Manis, P. Caboni, D. Hughes, A. Schapira. The potential role of monocytes a-synuclein and lipids as predictors of PD. [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/the-potential-role-of-monocytes-a-synuclein-and-lipids-as-predictors-of-pd/. Accessed October 10, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-potential-role-of-monocytes-a-synuclein-and-lipids-as-predictors-of-pd/