Neurofilament Light Protein Predicts Disease Progression in Idiopathic REM Sleep Behavior Disorder

Abstract

Background: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is increasingly recognized as a manifestation preceding the α-synucleinopathies like Parkinson’s disease (PD). Neurofilament light chain (NfL) have been reported to be higher in synucleinopathies as a sign of neurodegeneration. Objective: To evaluate whether plasma NfL is valuable in reflecting cognitive and motor status in iRBD and PD with a premorbid history of RBD (PDRBD), and predicting disease progression in iRBD. Methods: Thirty-one patients with iRBD, 30 with PDRBD, and 18 healthy controls were included in the cross-sectional and prospective study. Another cohort from the Parkinson’s Progression Markers Initiative (PPMI) dataset was enrolled for verification analysis. All patients received evaluations of cognitive, motor, and autonomic function by a battery of clinical tests at baseline and follow-up. Blood NfL was measured by the Quanterix Simoa HD-1. Results: In our cohort, 26 patients with iRBD completed the follow-up evaluations, among whom eight (30.8%) patients displayed phenoconversion. Baseline plasma NfL cutoff value of 22.93 pg/mL performed best in distinguishing the iRBD converters from non-converters (sensitivity: 75.0%, specificity: 83.3%, area under the curve: 0.84). Cognitive and motor function were significantly correlated with NfL levels in PDRBD (correlation coefficients: –0.379, 0.399; respectively). Higher baseline NfL levels in iRBD were significantly associated with higher risks for cognitive, motor, autonomic function progression, and phenoconversion at follow-up (hazard ratios: 1.069, 1.065, 1.170, 1.065; respectively). The findings were supported by the PPMI dataset. Conclusion: Plasma NfL is valuable in reflecting disease severity of PDRBD and predicting disease progression and phenoconversion in iRBD.

Plasma biomarkers of neurodegeneration in patients with Parkinson’s disease and dementia with Lewy bodies and at-risk individuals of Lewy body disease in the NaT-PROBE cohort

“…[38] Another study reported that higher baseline NfL levels in patients with idiopathic RBD was associated with worsening cognitive, motor, and autonomic functions and a higher risk of phenoconversion. [11] The present study demonstrated that plasma NfL levels were significantly elevated in the PD, DLB, and high-risk groups compared with those in the low-risk group. In patients with PD, those classified as N+ had worse scores on the MoCA-J, Hoehn and Yahr, MDS-UPDRS III, SCOPA-AUT, BDI-II, PDQ-39, and QUIP scales than those classified as N−, suggesting that plasma NfL levels are related to cognitive function, and motor and non-motor symptoms.…”

“…[6, 7] In addition, plasma neurofilament light chain (NfL) is regarded as a reliable biomarker for various neurodegenerative diseases. [8] Although recent studies have examined AD-related plasma biomarkers in patients with PD and DLB [9, 10] and plasma NfL in patients with idiopathic RBD,[11, 12] a detailed study on AD comorbidity in the prodromal phase of LBD is lacking.…”

Rapid eye movement sleep behavior disorder and its relation to Parkinson's disease: The potential of graph measures as brain biomarkers to identify the underlying physiopathology of the disorder

“…A biomarker is a measurable characteristic indicating normal or pathogenic biological processes or pharmacological responses to therapeutic drugs (Miglis et al, 2021). Biomarkers used for diagnosis of and fMRI), and genetic biomarker (GBA variants, SNCA, TMEM175) (Bramich et al, 2022;Gnarra et al, 2023;Zhang et al, 2023).…”

“…A biomarker is a measurable characteristic indicating normal or pathogenic biological processes or pharmacological responses to therapeutic drugs (Miglis et al., 2021 ). Biomarkers used for diagnosis of iRBD patients include neurophysiological (polysomnography, actigraphy, electroencephalogram), clinical (hyposmia, cognitive dysfunction, visual dysfunction, motor function, autonomic function) and biological biomarker (blood test, CSF, tissue biopsy), neuroimaging (positron emission tomography [PET], single‐photon emission computed tomography [SPECT], structural magnetic resonance imaging [MRI], DWI and fMRI), and genetic biomarker (GBA variants, SNCA, TMEM175) (Bramich et al., 2022 ; Gnarra et al., 2023 ; Zhang et al., 2023 ).…”

Tackling the usefulness of neurofilament light chain in multiple system atrophy: diagnostic and prognostic perspectives

“…This prospective and longitudinal study provides an extra level of confidence and moves the field forward in the role of NfL as a supportive biomarker in the diagnosis of MSA, which has been recently added to the 2022 Movement Disorder Society criteria [6]. This may be particularly helpful in patients in the prodromal stages of disease, such as those with rapid eye movement (REM) sleep behavior disorder (RBD) and pure autonomic failure (PAF) [7,8]. However, other studies have also reported high NfL-c levels in patients with progressive supranuclear palsy (PSP) [9,10], and to a lesser extent in dementia with Lewy bodies (DLB) [11,12], which could represent up to 30% of MSA misdiagnosis in autopsy series [13,14].…”