Baseline Cerebrospinal Fluid α-Synuclein in Parkinson's Disease Is Associated with Disease Progression and Cognitive Decline

Abstract

Biomarkers are increasingly recognized as tools in the diagnosis and prognosis of neurodegenerative diseases. No fluid biomarker for Parkinson’s disease (PD) has been established to date, but α-synuclein, a major component of Lewy bodies in PD and dementia with Lewy bodies (DLB), has become a promising candidate. Here, we investigated CSF α-synuclein in patients with PD (n = 28), PDD (n = 8), and DLB (n = 5), applying an electrochemiluminescence immunoassay. Median values were non-significantly (p = 0.430) higher in patients with PDD and DLB (287 pg/mL) than in PD (236 pg/mL). A group of n = 36 primarily non-demented patients with PD and PDD was clinically followed for up to two years. A higher baseline α-synuclein was associated with increases in Hoehn and Yahr classifications (p = 0.019) and Beck Depression Inventory scores (p < 0.001) as well as worse performance in Trail Making Test A (p = 0.017), Trail Making Test B (p = 0.043), and the Boston Naming Test (p = 0.002) at follow-up. Surprisingly, higher levels were associated with a better performance in semantic verbal fluency tests (p = 0.046). In summary, CSF α-synuclein may be a potential prognostic marker for disease progression, affective symptoms, and executive cognitive function in PD. Larger-scaled studies have to validate these findings and the discordant results for single cognitive tests in this exploratory investigation.

Keywords: Parkinson’s disease; alpha-synuclein; biomarker; cerebrospinal fluid; dementia; dementia with Lewy bodies.

Figure 1

Comparison of baseline data between diagnostic groups. Box Plot of CSF α-synuclein levels in Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), and dementia with Lewy bodies (DLB), left panel. In the right panel, differences in mean values and p-values from group comparisons between PD and Lewy body disease with dementia (LBDD) are displayed.

Figure 2

Association of α-synuclein with disease progression and affective symptoms in PD. Correlations from mixed linear regression are displayed by scatter plots with regression lines at baseline (1, red plot), 6 months (2, green plot), 12 months (3, turquoise plot), and 24 months (4, purple plot). Estimates, t-values, and p-values refer to the correlation of Hoehn and Yahr (H + Y) stage (A) and Beck Depression Inventory (BDI) scores (B) with α-synuclein (αSyn), changes in the stage/score over time (time), and to the correlation of baseline CSF α-synuclein with changes in stage/score over time (αSyn:time).

Figure 3

Association of α-synuclein with cognitive test performance. Correlations from mixed linear regression are displayed through scatter plots with regression lines at baseline (1, red plot), 6 months (2, green plot), 12 months (3, turquoise plot), and 24 months (4, purple plot). Estimates, t-values, and p-values refer to the correlation of results from the Boston Naming Test (BNT) (A), Semantic verbal fluency (SemFlu) (B), Trail Making Test A (TMT A) (C), and Trail Making Test B (TMT B) (D) with α-synuclein (αSyn), changes over time (time), and to the correlation of baseline CSF α-synuclein with changes in stage/score over time (αSyn:time).

Figure 3

Association of α-synuclein with cognitive test performance. Correlations from mixed linear regression are displayed through scatter plots with regression lines at baseline (1, red plot), 6 months (2, green plot), 12 months (3, turquoise plot), and 24 months (4, purple plot). Estimates, t-values, and p-values refer to the correlation of results from the Boston Naming Test (BNT) (A), Semantic verbal fluency (SemFlu) (B), Trail Making Test A (TMT A) (C), and Trail Making Test B (TMT B) (D) with α-synuclein (αSyn), changes over time (time), and to the correlation of baseline CSF α-synuclein with changes in stage/score over time (αSyn:time).