Objective: 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 Parkinson’s disease (PD) and Controls.

Background: It is important to understand the temporal changes in biomarkers in order to improve early diagnosis in PD, Still, few longitudinal CSF biomarker studies have yet been performed. Cross-sectional studies have evaluated the diagnostic potential of α-synuclein (α-syn), neurofilament light (NFL), tau, phosphorylated tau (P-tau) and amyloid β (Aβ) for PD-related disorders. CSF levels of α-syn have, compared with controls, been found to be decreased in patients with PD. On the other hand, CSF α-syn show a very marked increase in disorders with rapid neurodegeneration such as Creutzfeldt-Jakob disease, and also a clear increase in Alzheimer’s disease compared with both controls and patients with PD indicating that α-syn levels in CSF reflects neuronal degeneration.

Methods: We included 63 patients with PD (non-demented) 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-syn. The levels of CSF α-syn, tau, P-tau, NFL, and YKL-40, but not β-amyloid42, increased in CSF over 2 years in PD. When studying patients with short disease duration (≤5y disease duration) and patients with long disease duration (>5y disease duration) separately, we found that α-syn and tau only increased in the PD group with long disease duration. In the control group there were no significant changes over time in CSF biomarkers. In the PD group, an increase in P- 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.

Conclusions: CSF biomarkers reflecting Lewy body pathology and neurodegeneration (α-syn), neuronal degeneration (tau, P-tau and NFL) and inflammation (YKL-40) increase significantly over 2 years in PD. CSF levels of α-syn and tau correlate, remain stable in the early symptomatic phase of PD but increase in the later phase. We hypothesise that CSF α-syn levels might increase as a result of more intense neurodegeneration in PD with long disease duration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-measurements-of-cerebrospinal-fluid-biomarkers-in-parkinsons-disease/