Associations among blood biomarkers, clinical subtypes, and prognosis in Parkinson's disease.

Background: Early identification of the poor prognosis subtype by surrogate markers would be advantageous for selecting treatments for Parkinson's disease (PD). The aim of the present study was to test whether plasma neurofilament light chain (NF-L), total tau (t-tau), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), fatty acid-binding protein 3 (FABP3), and phosphorylated tau (p-tau) can be used as prognostic biomarkers in PD. Methods: In the present study, both retrospective and prospective studies were performed. Plasma samples at baseline from 81 PD patients were included in the prospective study. Plasma samples at baseline from 60 patients who underwent cognitive assessment were subjected to the hierarchical cluster analysis for a retrospective study. Results: On the basis of the results of the cluster analysis, patients were classified into three groups: groups (G)1, G2 and G3. Individuals in the G1 cluster, who had an older age at onset and were prone to early progression with dementia, had significantly greater plasma NF-L levels than those in the G3 cluster, who did not present with dementia at an early stage. A Cox proportional hazards regression model adjusted for age and sex revealed that high NF-L and UCH-L1 levels at baseline predicted the four future milestones (i.e., nursing care, dysphagia, wheelchair use, and repeated falls), and high plasma t-tau at baseline predicted future dysphagia. Conclusions: Although further studies with a larger number of patients will be required, plasma NF-L may be a useful biomarker for identifying the rapidly progressive subtype of PD, and plasma NF-L and UCH-L1 may serve as biomarkers of overall PD prognosis, whereas plasma t-tau could be a biomarker for future dysphagia in PD.