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

Foulds PG, Diggle P, Mitchell JD, Parker A, Hasegawa M, Masuda-Suzukake M, Mann DM, Allsop D - Sci Rep (2013)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, University of Lancaster, Lancaster, LA1 4AY, UK.

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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Related in: MedlinePlus

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.
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f2: 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.

Mentions: Figure 1 shows representative examples of standard curves for each of the two different immunoassays. Empirical distributions of the plasma α-syn concentrations for both assays were highly skewed on the original scale, and so log-transformed data were used for all of the cross-sectional and longitudinal statistical analyses described below. Figure 2 presents dot-plots of the baseline data on PD cases and controls pertaining to each assay. In the case of cross-sectional analysis of the PD samples, we have used the blood sample taken at the first visit as the baseline value, whereas data for single blood samples only were available from the controls. To investigate the potential of α-syn as a means of discriminating between patients with PD and healthy controls, we determined whether there was any significant difference between the average level of α-syn (on the logarithmic scale) across patients and controls, within the two different α-syn assays. Using a standard two-sample t test on log-transformed concentrations, there was found to be no significant difference between the average levels of PD patients and healthy controls for ‘total α-syn’ (p = 0.058), whereas the average level of phosphorylated α-syn was found to be significantly higher for the PD patients than for the healthy controls (p = 0.012). The mean levels for each assay, on the original scale, are given in table 1. It can be seen that the mean level of phosphorylated α-syn was approximately 5-fold higher in the PD samples (756.8 ng/ml) than in the healthy controls (143.4 ng/ml).


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

Foulds PG, Diggle P, Mitchell JD, Parker A, Hasegawa M, Masuda-Suzukake M, Mann DM, Allsop D - Sci Rep (2013)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756331&req=5

f2: 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.
Mentions: Figure 1 shows representative examples of standard curves for each of the two different immunoassays. Empirical distributions of the plasma α-syn concentrations for both assays were highly skewed on the original scale, and so log-transformed data were used for all of the cross-sectional and longitudinal statistical analyses described below. Figure 2 presents dot-plots of the baseline data on PD cases and controls pertaining to each assay. In the case of cross-sectional analysis of the PD samples, we have used the blood sample taken at the first visit as the baseline value, whereas data for single blood samples only were available from the controls. To investigate the potential of α-syn as a means of discriminating between patients with PD and healthy controls, we determined whether there was any significant difference between the average level of α-syn (on the logarithmic scale) across patients and controls, within the two different α-syn assays. Using a standard two-sample t test on log-transformed concentrations, there was found to be no significant difference between the average levels of PD patients and healthy controls for ‘total α-syn’ (p = 0.058), whereas the average level of phosphorylated α-syn was found to be significantly higher for the PD patients than for the healthy controls (p = 0.012). The mean levels for each assay, on the original scale, are given in table 1. It can be seen that the mean level of phosphorylated α-syn was approximately 5-fold higher in the PD samples (756.8 ng/ml) than in the healthy controls (143.4 ng/ml).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, University of Lancaster, Lancaster, LA1 4AY, UK.

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.

Show MeSH
Related in: MedlinePlus