Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson's Disease

Abstract

Objective: The purpose of this study was to investigate whether cerebrospinal fluid (CSF) levels of tau, phosphorylated tau, β-amyloid42 , α-synuclein, neurofilament light, and YKL-40 change over time and if changes correlate with motor progression and/or cognitive decline in patients with PD and controls.

Methods: We included 63 patients with PD (nondemented) and 21 neurologically healthy controls from the prospective and longitudinal Swedish BioFINDER study, all of whom had clinical assessments and lumbar punctures at baseline and after 2 years.

Results: CSF tau levels correlated strongly with α-synuclein. The levels of CSF α-synuclein, tau, phosphorylated tau, neurofilament light, and YKL-40, but not β-amyloid42 , increased in CSF over 2 years in PD. No changes were seen in the control group. Studying patients with a short disease duration ( ≤ 5 years) and patients with a long disease duration ( > 5 years) separately, α-synuclein and tau only increased in the PD group with long disease duration. In the PD group, an increase in phosphorylated tau over 2 years correlated with faster motor progression and faster cognitive decline. An increase in YKL-40 over 2 years correlated with faster cognitive decline.

Conclusion: CSF biomarkers reflecting Lewy body pathology and neurodegeneration (α-synuclein), neuronal degeneration (tau, phosphorylated tau, and neurofilament light), and inflammation (YKL-40) increase significantly over 2 years in PD. CSF levels of α-synuclein and tau correlate and remain stable in the early symptomatic phase of PD but increase in the later phase. We hypothesize that CSF α-synuclein levels might increase as a result of more intense neurodegeneration in PD with long disease duration. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; biomarkers; cerebrospinal fluid; longitudinal; prognosis.

Figure 1

Percent change in CSF levels of amyloid β₄₂ (Aβ₄₂), α‐synuclein (α‐syn), tau, phosphorylated tau (P‐tau), neurofilament light (NFL), and YKL‐40 over 2 years. Scatter dots of change in percentages in CSF levels of Aβ₄₂, tau, P‐tau, α‐syn, NFL, and YKL‐40 over 2 years. Lines represent means and standard deviations. One data point for P‐tau at 200% and 1 data point for NFL at 276% are outside the axis limit.

Figure 2

Percent change in CSF levels of α‐synuclein (α‐syn) in PD with short and long disease duration over 2 years. Levels of CSF α‐syn increase in the PD group with long disease duration over 2 years but not in the PD group with long disease duration. Scatter dots of change in percentages in CSF levels of α‐syn in PD with short and long disease durations. Lines represent means and standard deviations.

Figure 3

Correlations of changes CSF P‐tau with change in UPDRS III and letter fluency and CSF YKL‐40 with change in letter fluency over 2 years. Correlations of change in CSF levels of P‐tau with change in UPDRS III (A) and letter fluency (B) in the PD group. Correlations of change in CSF levels of YKL‐40 with change in letter fluency (C) in the PD group. Solid line indicates a linear regression, and dotted lines are 95% confidence intervals.