A longitudinal study on α-synuclein in blood plasma as a biomarker for Parkinson's disease - PubMed (original) (raw)

A longitudinal study on α-synuclein in blood plasma as a biomarker for Parkinson's disease

Penelope G Foulds et al. Sci Rep. 2013.

Abstract

There have been no longitudinal studies on α-synuclein as a potential biomarker for the progression of Parkinson's disease (PD). Here, blood plasma 'total α-synuclein' and 'Ser-129 phosphorylated α-synuclein' were assayed at 4-6 monthly intervals from a cohort of 189 newly-diagnosed patients with PD. For log-transformed data, plasma total α-synuclein levels increased with time for up to 20 yrs after the appearance of initial symptoms (p = 0.012), whereas phosphorylated α-synuclein remained constant over this same period. The mean level of phosphorylated α-synuclein, but not of total α-synuclein, was higher in the PD plasma samples taken at first visit than in single samples taken from a group of 91 healthy controls (p = 0.012). Overall, we conclude that the plasma level of phosphorylated α-synuclein has potential value as a diagnostic tool, whereas the level of total α-synuclein could act as a surrogate marker for the progression of PD.

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Figures

Figure 1

Figure 1. Examples of standard curves obtained for total α-syn (A) and phosphorylated α-syn (B).

These are representative curves, each obtained from a single ELISA plate.

Figure 2

Figure 2. Baseline measurements of log-transformed α-syn plasma concentrations in PD patients and normal healthy controls.

Left-hand panel shows log-transformed phosphorylated α-syn, right-hand panel log-transformed total α-syn, horizontal lines denote sample means.

Figure 3

Figure 3. Fitted time-trends (solid lines) and 95% pointwise confidence intervals (dashed lines) for repeated measurements of log-transformed α-syn plasma concentrations obtained from patients with PD, plotted as time since onset of initial symptoms.

P-values refer to Wald tests of the hypothesis of no time-trend. Note that the level of phosphorylated α-syn does not change significantly with disease progression, whereas total α-syn shows a significant increasing time-trend.

Figure 4

Figure 4. ROC curve to evaluate the utility of plasma phosphorylated α-syn levels in discriminating patients with PD from healthy controls.

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