Objective: Reliable blood biomarkers for identifying the Parkinson’s disease (PD) spectrum and reflecting disease severity remain limited. We investigated whether multiple serum biomarkers could differentiate the PD continuum and associated clinical severity.

Background: Parkinson’s disease (PD) is characterized by a broad spectrum of motor and non-motor symptoms. Despite this clinical heterogeneity, reliable biomarkers that reflect overall disease burden and stage remain limited. Fluid biomarkers reflecting specific pathophysiological processes have shown promise in both diagnosis and prognosis in PD. However, the role of serum biomarkers reflecting current disease severity or disease stage in PD remains uncertain.

Method: We analyzed serum concentrations of five biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, ubiquitin C-terminal hydrolase L1 (UCHL1), and brain-derived neurotrophic factor (BDNF)—using the ultrasensitive Single Molecule Array (Simoa) platform. A total of 206 participants were included, comprising 37 normal controls (NC), 24 patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), and 145 patients with PD.

Results: Serum NfL and GFAP levels were significantly higher in PD than in NC, whereas BDNF levels were lower in PD. The RBD group showed numerically intermediate levels without significant differences. Within PD, NfL, GFAP, tau, UCHL1 showed increasing trends across higher categories of motor and cognitive severity, whereas BDNF showed a decreasing trend. NfL was the only biomarker independently associated with motor severity (Hoehn and Yahr stage and Unified Parkinson’s Disease Rating Scale Part III scores) and global cognition.

In ordinal logistic regression models differentiating the PD spectrum (NC-RBD-PD), GFAP showed the best performance among single biomarkers, while combination models did not outperform GFAP alone. For PD disease severity, NfL consistently discriminated motor and cognitive stages, and combination models did not exceed its performance.

Conclusion: GFAP best differentiated the PD disease spectrum, whereas NfL consistently reflected motor and cognitive severity of PD. These serum biomarkers may provide complementary information for stratifying patients across the PD continuum.

Figure 1. Box plot of Biomarkers

Figure 2. AUC Heatmap

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multiplexed-serum-biomarkers-for-differentiating-the-parkinsons-disease-continuum-and-disease-severity/