Objective: To investigate plasma alpha-synuclein levels in PD using ultra-sensitive protein detection technology, and to determine the association of plasma alpha-synuclein with cognitive, motor and disability scores.

Background: Discriminating between healthy subjects and Parkinson disease (PD) patients using blood-based biomarkers has been limited by the very low concentrations of circulating alpha-synuclein in blood that remain difficult to accurately detect and quantify using existing methods.

Methods: 224 subjects were included in this study (52 gender-matched controls and 172 PD patients). Plasma alpha-synuclein was measured using Quanterix’s Single Molecule Array (Simoa) technology. All subjects underwent tests of global cognition (mini-mental state examination, MMSE), motor evaluation using the Unified Parkinson’s Disease Rating Scale (UPDRS) and disability scoring on the Hoehn & Yahr (H&Y) scale.

Results: Plasma alpha-synuclein levels were significantly higher in PD than controls (15556.2 vs 13122.8 pg/ml, p=0.042), after adjusting for age and gender. In PD patients, plasma alpha-synuclein levels did not vary significantly by disease stage (H&Y 1-2 vs H&Y 2.5-5, p=0.26), nor by UPDRS motor scores (p=0.875). Synuclein levels in PD with lower cognitive scores (MMSE<=25) were significantly higher than in controls (p=0.015, Bonferroni adjusted p=0.044); while levels in PD with MMSE>25 were not significantly different compared to controls (p=0.063, Bonferroni adjusted p=0.190). ROC analysis revealed that plasma alpha-synuclein levels could differentiate PD from controls (AUC= 0.597, 95% CI =0.507 – 0.687) and PD with MMSE<=25 from controls (AUC= 0.627, 95% CI =0.519 – 0.735). In PD patients carrying the reported Asian leucine-rich repeat kinase 2 (LRRK2) risk variants S1647T, G2385P and R1628P, plasma alpha-synuclein levels did not differ significantly between carriers and non-carriers. Notably, in controls, carriers of the reported Asian LRRK2 protective variants (N551K and R1398H in linkage disequilibrium) demonstrated a non-significant trend towards lower plasma synuclein levels than in non-carriers; whereas carriers of LRRK2 risk variants (S1647T, R1628P and G2385P) showed higher alpha-synuclein levels than in non-carriers (p=0.421, after controlling for age and gender).

Conclusions: The single molecular array method of quantifying levels of plasma alpha-synuclein may act as a potential biomarker for Parkinson’s disease, particularly in patients with lower cognitive scores. Further studies are required to validate these findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levels-of-plasma-alpha-synuclein-as-measured-using-single-molecule-array-technology-is-higher-in-parkinsons-disease-compared-to-controls-and-is-not-influenced-by-lrrk2-genotype/