Objective: The objective of this study was to assess if soluble urokinase-type plasminogen activator receptor (SuPAR) is elevated in patients with Parkinson’s disease (PD).

Background: SuPAR is a chronic marker of inflammation and immune activation. This inflammatory biomarker that has been shown to be associated with advanced aging¹ and increased mortality in various patient groups including those with chronic kidney disease, cardiovascular disease, and hospitalized patients^{2, 3}, but has never been studied in patients with PD.

Method: In this observational case control study, patients with varying stages of PD (early n=25, HY 1-3 n=25, and HY 4-5 n=10) and healthy controls (n=36) were recruited from an outpatient movement disorder clinic and underwent clinical assessments including SF-36, MOCA, MDS-UPDRS, HAM-D, general and neurological exam. Subjects were excluded if they had an infection, active cancer, or if they were receiving treatment with immunotherapy. SuPAR was analyzed using Quantikine® ELISA Human SuPAR Immunoassay and cytokines were analyzed using Luminex® Corporation Human High Sensitivity T-cell Magnetic Bead Panel. These were collected during clinical assessments. For two groups comparisons, t test, rank sum test or chi-square test were used. For four groups comparisons, ANOVA, Kruskal-Wallis test or chi-square test were used.

Results: Healthy controls (n=36) and subjects with PD (n=60) respectively had a mean age of 63.25 (IQR 8.83 vs 65.93 years old (IQR 10.06); p=0.18), minority were women (17 (47.22%) vs 25 (41.67%); p=0.6), and majority were white (33 (91.67%) vs 60 (100.00%); p=0.05). Subjects with PD (HY4-5) had elevated SuPAR compared to healthy controls, and the highest levels were observed within patients with more advanced PD (4.51 ng/mL (IQR 1.30) compared to 3.36 ng/mL, (IQR 1.03); p=0.004). However, when controlling for age as a covariate in a linear regression analysis, this difference was no longer significant. TNF-alpha was overall higher in healthy controls than in older PD subjects with more advanced diseased (11.33 pg/mL (IQR 4.91) vs HY 4-5 group 7.1 pg/mL (IQR 3.9); p=0.01). However, there were no differences in the levels of IL-10, IL-17a, IL-1beta, IL-2, IL-21, IL-4, IL-23, or IL-6.

Conclusion: Patient’s with PD, especially advanced PD based on HY staging, had elevated SuPAR, but this was driven in part by age. This study supports the utility of SuPAR as a marker for aging.

References: 1. Rasmussen LJH, Caspi A, Ambler A, Danese A, Elliott M, Eugen-Olsen J, et al. Association Between Elevated suPAR, a New Biomarker of Inflammation, and Accelerated Aging. The Journals of Gerontology: Series A. 2020;76(2):318-27. 2. Haupt TH, Petersen J, Ellekilde G, Klausen HH, Thorball CW, Eugen-Olsen J, et al. Plasma suPAR levels are associated with mortality, admission time, and Charlson Comorbidity Index in the acutely admitted medical patient: a prospective observational study. Critical care (London, England). 2012;16(4):R130. 3. Koller L, Stojkovic S, Richter B, Sulzgruber P, Potolidis C, Liebhart F, et al. Soluble Urokinase-Type Plasminogen Activator Receptor Improves Risk Prediction in Patients With Chronic Heart Failure. JACC Heart failure. 2017;5(4):268-77.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/soluble-urokinase-type-plasminogen-activator-receptor-supar-in-patients-with-parkinsons-disease/