Plasma pS129-α-Synuclein Is a Surrogate Biofluid Marker of Motor Severity and Progression in Parkinson’s Disease

• Main Authors: Chin-Hsien Lin, Huei-Chun Liu, Shieh-Yueh Yang, Kai-Chien Yang, Chau-Chung Wu, Ming-Jang Chiu
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Journal of Clinical Medicine
• Subjects: parkinson’s disease; biomarker; α-synuclein; ps129-α-synuclein; motor severity
• Online Access: https://www.mdpi.com/2077-0383/8/10/1601

Phosphorylated &#945;-synuclein accounts for more than 90% of &#945;-synuclein found in Lewy bodies of Parkinson&#8217;s disease (PD). We aimed to examine whether plasma Ser129-phosphorylated &#945;-synuclein (pS129-&#945;-synuclein) is a surrogate marker of PD progression. This prospective study enrolled 170 participants (122 PD patients, 68 controls). We measured plasma levels of total and pS129-&#945;-synuclein using immunomagnetic reduction-based immunoassay. PD patients received evaluations of motor and cognition at baseline and at a mean follow-up interval of three years. Changes in the Movement Disorder Society revision of the Unified Parkinson&#8217;s Disease Rating Scale motor score (MDS-UPDRS part III) and Mini-Mental State Examination (MMSE) score were used to assess motor and cognition progression. Our results showed that plasma levels of total and pS129-&#945;-synuclein were significantly higher in PD patients than controls (total: 1302.3 &#177; 886.6 fg/mL vs. 77.8 &#177; 36.6 fg/mL, <i>p</i> &lt; 0.001; pS129-&#945;-synuclein: 12.9 &#177; 8.7 fg/mL vs. 0.8 &#177; 0.6 fg/mL, <i>p</i> &lt; 0.001), as was the pS129-&#945;-synuclein/total &#945;-synuclein ratio (2.8 &#177; 1.1% vs. 1.1 &#177; 0.6%, <i>p</i> = 0.01). Among PD patients, pS129-&#945;-synuclein levels were higher with advanced motor stage (<i>p</i> &lt; 0.001) and correlated with MDS-UPDRS part III scores (<i>r</i> = 0.27, 95% CI: 0.09&#8722;0.43, <i>p</i> = 0.004). However, we found no remarkable difference between PD patients with and without dementia (<i>p</i> = 0.75). After a mean follow-up of 3.5 &#177; 2.1 years, PD patients with baseline pS129-&#945;-synuclein &gt; 8.5 fg/mL were at higher risk of motor symptom progression of at least 3 points in the MDS-UPDRS part III scores than those with pS129-&#945;-synuclein &lt; 8.5 fg/mL (<i>p</i> = 0.03, log rank test). In conclusion, our data suggest that plasma pS129-&#945;-synuclein levels correlate with motor severity and progression, but not cognitive decline, in patients with PD.