Objective: We aimed  to investigate biomarkers of inflammation and neuroaxonal damage in people with isolated REM sleep behaviour disorder (iRBD) compared to controls, and understand potential correlation with clinical symptom severity in people with iRBD.

Background: iRBD is a known prodrome of Parkinson’s disease (PD), which can occur years prior to motor symptom onset [1]. Inflammation has been implicated early in PD; [2,3] thus inflammatory cytokines may provide a unique window into events occurring during prodromal PD. Neurofilament light chain (NfL) is a marker of neuro-axonal damage, and has been related to conversion to PD in iRBD patients [4]. Together these may offer the potential to elucidate early biomarkers of PD.

Method: 28 polysomnography confirmed iRBD patients and 27 age- and sex-matched controls underwent blood sampling and clinical assessment. Plasma levels of inflammatory proteins (CRP, IL-6, TNF-α, IFN-γ, IL-1β) and NfL were measured using the Meso Scale Discovery (MSD) platform. The Mann-Whitney U test was used to compare iRBD and control groups and linear regression was used to correlate clinical symptom severity with biomarker levels.

Results: People with iRBD had elevated levels of IL-6, TNF-α and NfL in plasma (p=0.038, p=0.053 and p=0.040, respectively), indicating higher levels of peripheral inflammation and neuro-axonal damage. In subgroup analysis, iRBD patients with mild Parkinsonian signs had higher NfL values than those without (p=0.059). Weak correlation was seen between plasma NfL and motor symptoms, quantified by UPDRS Part 3 scores (R=0.37, p=0.056), which was strengthened by using objective motor tests, such as the Timed Up and Go (TUG) test (R=0.51, p=0.006), and more subtle motor tests such as the Bradykinesia Akinesia Incoordination (BRAIN) test (R=-0.56, p=0.003). No correlations were observed between plasma biomarkers and cognitive or autonomic symptom severity, or between plasma biomarkers and clinical features in the control group.

Conclusion: These data support the presence of peripheral inflammation early on in the PD disease process, and suggest that elevated plasma NfL may be a marker of early PD and motor features in iRBD. Investigative studies of this size should hopefully fuel further large-scale longitudinal studies of blood-based biomarkers of peripheral inflammation and neuronal damage in prodromal PD patients.

References: [1] Postuma, Ronald B., Jean-Francois Gagnon, Josie-Anne Bertrand, Daphné Génier Marchand, and Jacques Y. Montplaisir. “Parkinson Risk in Idiopathic REM Sleep Behavior Disorder: Preparing for Neuroprotective Trials.” Neurology 84, no. 11 (March 17, 2015): 1104–13.
[2] Zhang, Hui, Ting Wang, Yuan Li, Wei Mao, Shuwen Hao, Zhaoyang Huang, Piu Chan, and Yanning Cai. “Plasma Immune Markers in an Idiopathic REM Sleep Behavior Disorder Cohort.” Parkinsonism & Related Disorders 78 (September 1, 2020): 145–50.
[3] Kim, Ryul, Jee-Young Lee, Han-Joon Kim, Yu Kyeong Kim, Hyunwoo Nam, and Beomseok Jeon. “Serum TNF-α and Neurodegeneration in Isolated REM Sleep Behavior Disorder.” Parkinsonism & Related Disorders 81 (December 1, 2020): 1–7.
[4] Wilke, Carlo, Marcia Cristina Teixeira dos Santos, Claudia Schulte, Christian Deuschle, Dieter Scheller, Moira Verbelen, Kathrin Brockmann, et al. “Intraindividual Neurofilament Dynamics in Serum Mark the Conversion to Sporadic Parkinson’s Disease.” Movement Disorders 35, no. 7 (2020): 1233–38.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-biomarkers-in-irbd-patients-serve-as-potential-markers-of-early-pd-and-motor-severity/