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.

Arylsulfatase A (ASA) in Parkinson’s Disease: From Pathogenesis to Biomarker Potential

“…Notably, a very recent study has demonstrated an interesting relationship between ASA plasma levels and PD progression [ 52 ]. In particular, the early PD subgroup characterized by shorter disease duration and lower UPDRS motor scores had higher ASA plasma levels, as compared to the late PD subgroup and healthy controls, independent of age, gender and MMSE scores [ 52 ].…”

“…Notably, a very recent study has demonstrated an interesting relationship between ASA plasma levels and PD progression [ 52 ]. In particular, the early PD subgroup characterized by shorter disease duration and lower UPDRS motor scores had higher ASA plasma levels, as compared to the late PD subgroup and healthy controls, independent of age, gender and MMSE scores [ 52 ]. Plasma ASA levels were graphically represented as an inverted U-shape in regard to the duration of the disease, reaching a peak at approximately 2 years of disease duration [ 52 ].…”

“…In particular, the early PD subgroup characterized by shorter disease duration and lower UPDRS motor scores had higher ASA plasma levels, as compared to the late PD subgroup and healthy controls, independent of age, gender and MMSE scores [ 52 ]. Plasma ASA levels were graphically represented as an inverted U-shape in regard to the duration of the disease, reaching a peak at approximately 2 years of disease duration [ 52 ]. In the early PD subgroup, plasma ASA levels were also positively correlated with UPDRS motor scores and striatal dopamine depletion as evaluated by DATscan [ 52 ].…”

“…Plasma ASA levels were graphically represented as an inverted U-shape in regard to the duration of the disease, reaching a peak at approximately 2 years of disease duration [ 52 ]. In the early PD subgroup, plasma ASA levels were also positively correlated with UPDRS motor scores and striatal dopamine depletion as evaluated by DATscan [ 52 ]. Other demographic or clinical parameters, such as age at disease onset, education years or MMSE scores, were not associated with plasma ASA levels [ 52 ].…”

“…In the early PD subgroup, plasma ASA levels were also positively correlated with UPDRS motor scores and striatal dopamine depletion as evaluated by DATscan [ 52 ]. Other demographic or clinical parameters, such as age at disease onset, education years or MMSE scores, were not associated with plasma ASA levels [ 52 ]. These findings partially agree with the results of the abovementioned study which showed that PD patients without dementia displayed increased ASA levels, compared to PD with dementia or healthy controls [ 31 ].…”