Objective: To analyze changes in levels of four distinct biomarkers in drug-naïve Parkinson’s disease (PD) subjects in cerebrospinal fluid (CSF) over 6- and 12 mo of follow-up we describe how these changes relate to clinical measures, and identify factors that may influence biomarker changes.

Background: Longitudinal changes in biomarkers during natural history studies of PD may provide indices of biological processes related to disease activity or progression. CSF protein biomarkers reflect the underlying pathology proximal to the disease and may, upon showing longitudinal dynamics, assist the design of clinical trials aimed at neuroprotection in PD.

Methods: Longitudinal study on recently diagnosed PD subjects and healthy controls of the international multicenter Parkinson Progression Marker Initiative. CSF levels of α-synuclein (α-syn), total and phosphorylated tau (t-tau and p-tau) protein and β-amyloid 1-42 (Aβ42) were measured at baseline, 6 and 12 mo, in 173 PD subjects with documented putaminal dopaminergic deficit at baseline and 112 age and gender matched healthy controls (HC). Changes in CSF biomarkers over time were analyzed in each group. Baseline clinical and demographic variables, PD medications, neuroimaging and genetic variables were evaluated as potential predictors of CSF biomarker changes. The relationship between changes in CSF biomarkers and changes in clinical indices was examined.

Results: CSF biomarkers generally remained stable over 6 and 12 mo. CSF Aβ42 showed a small but significant increase in PD and HC subjects from baseline to 12 mo. Total tau remained stable over time in all groups. P-tau levels increased slightly, more in PD than HC. While α-syn decreased slightly in PD it remained relatively stable in the controls. The ratios of p-tau/total tau and of total tau/ Aβ42 decreased over 12 mo in PD.

Conclusions: Markers of tau, p-tau, Aβ42 do not change dramatically with progression of PD, possibly because they originate from many types of neurons, not just those affected by PD. How α-syn gets into CSF during normal neuronal health and how this continues to do so during neurodegeneration is not clear, but these data suggest that it does change dramatically directly with degeneration of nigrostriatal terminals. Therefore, longer time intervals are needed to determine if the analytes studied here will reflect progression of PD and the emergence of more profound motor and non-motor symptoms while the search for delineate better progression markers for early PD need to be established.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-cerebrospinal-fluid-biomarkers-in-early-parkinsons-disease-and-healthy-controls/