Objective: We aim to investigated the relationship between glial markers and Parkinson’s disease.

Background: Neuronal α-Synuclein Disease (NSD) has recently been proposed as a framework for identifying biological anchors of Parkinson’s disease, encompassing neuronal α-synuclein (S) and dopaminergic dysfunction (D). However, the role of glial interactions in α-syn pathology remains poorly understood. In this study, we examined the association between glial markers and Parkinson’s disease pathophysiology.

Method: The Parkinson’s Progression Markers Initiative (PPMI) database was used to retrieve cerebrospinal fluid (CSF) glial biomarkers measures. Biological anchor S was assessed by Amprion-αS-SAA (Fig. 1a-d) and D as assessed with DaTscan visual interpretation and Putamen’s lowest SBR value. CSF GFAP, STREM2, YKL40 and S100 were measured using Roche NeuroTool Kit. Clinical and cognitive variables collected included sex, years of education, Hoehn & Yahr scale (HY), and the total MDS-UPDRS data. Group comparisons were analyzed using Chi-squared test and ANOVA. General linear models adjusted for age were conducted to evaluate the association of glial markers, biological anchors, and HY. All statistical analyses were performed in R v4.

Results: A total of 268 individuals (67 controls and 201 PD) were evaluated (mean age 61.4±10.3 years, Tab. 1). S+D+ individuals had higher scores on total MDS-UPDRS (p < 0.001) and lower MOCA (p < 0.001) scores compared to S-D-. CSF YKL-40 levels were associated with S (beta = -0.37, p = 0.02) and D biological anchors (b = -0.37, p = 0.02, Fig. 2b) adjusted for age. CSF GFAP, S100B and sTREM2 were not associated with S or D (p > 0.05). When evaluating clinical symptoms of PD with HY, CSF YKL-40 was associated with HY scores (beta = -0.36, p = 0.02, Fig. 2c). However, in S+ individuals, only CSF GFAP levels showed a significant interaction with DaT putamen SBP levels and HY scores (beta = 0.65, p = 0.004).

Conclusion: CSF YKL-40 levels may reflect early events in PD’s neuronal alpha-synuclein pathological process. Additionally,, CSF GFAP levels may be associated with PD functional independence related to dopamine dysfunction in S+ individuals. Further studies may investigate the interaction between glial markers and biological anchors in PD.

Fig.1 | Methodology

Tab.1 | Demographics

Fig.2 | Statistical analysis

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MDS Abstracts - https://www.mdsabstracts.org/abstract/glial-interaction-with-parkinsonian-disorders-biomarkers-alpha-synuclein-dopaminergic-dysfunction-and-clinical-stages/