Changes in plasma arylsulfatase A level as a compensatory biomarker of early Parkinson's disease

Abstract

Lysosomal dysfunction has been associated with Parkinson's disease (PD). However, the activity of lysosomal enzymes is heterogeneously observed in PD. We investigated whether arylsulfatase A (ARSA) level can be used as a fluid biomarker of PD and can reflect disease progression. Plasma ARSA level was measured in 55 patients with early and drug-naïve PD, 13 patients with late PD, and 14 healthy controls. We compared the plasma ARSA level among the groups and assessed its correlation to clinical parameters and striatal dopamine transporter (DAT) activity. Plasma ARSA level was not correlated with age. The early PD group had higher plasma ARSA level than the control and late PD groups. In a generalized additive model including all patients with PD, the plasma ARSA level showed an inverted U-shape according to disease duration, peaking at 2.19 years. In patients with early PD, plasma ARSA level was positively correlated to parkinsonian motor score and negatively to striatal DAT activity. In summary, plasma ARSA level was elevated in early stage of PD, and elevated plasma ARSA level was correlated to the clinical and imaging markers of nigrostriatal degeneration. These results suggest that ARSA level is a potential biomarker of compensation in early PD.

Figure 1

(A) Group comparison of plasma ARSA levels. The post-hoc subgroup comparison was performed using the Bonferroni method. (B) Relationship between plasma ARSA level and disease duration. In all analyses, age, sex, and total K-MMSE score were used as covariates. ARSA, arylsulfatase A; AU, arbitrary unit; HC, healthy controls; K-MMSE, Korean version of the Mini-Mental State Examination; PD, Parkinson’s disease.

Figure 2

(A) Correlation between plasma ARSA level and the UPDRS motor score. (B) Correlation between plasma ARSA level and the striatal dopamine transporter activity. In all analyses, age, sex, and total K-MMSE score were used as covariates. ARSA, arylsulfatase A; AU, arbitrary unit; DAT, dopamine transporter; K-MMSE, Korean version of the Mini-Mental State Examination; PD, Parkinson’s disease; UPDRS, Unified Parkinson’s Disease Rating Scale.

Figure 3

Western blot images (cropped) of plasma ARSA levels. Western blot analysis of plasma ARSA levels was performed in healthy controls (N = 14), early Parkinson’s disease (PD) group (N = 55), and late PD group (N = 13).