Multimodal MRI correlates of elevated plasma NfL and GFAP in Parkinson’s disease with probable REM sleep behavior disorder

Abstract This study aimed to evaluate plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and structural and functional brain MRI alterations in Parkinson’s disease (PD) patients with REM sleep behavior disorder (RBD). We prospectively recruited 111 PD patients stratified into PD with probable RBD (PD-pRBD, n = 56) and PD without probable RBD (PD-npRBD, n = 55), plus healthy controls. We collected clinical data, plasma biomarkers, and 3T MRI scans to analyze gray matter volume via voxel-based morphometry, and resting-state amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC). PD-pRBD patients exhibited elevated plasma NfL and GFAP, which were positively associated with RBDQ-HK scores. They also showed right caudate atrophy, which was negatively correlated with RBD severity and with both plasma biomarkers. Additionally, this group exhibited altered ALFF in the occipital pole, anterior cingulate cortex and brainstem, along with disrupted frontotemporal, visual and auditory network connectivity. In conclusion, greater RBD symptom severity was associated with right caudate atrophy and distributed cortical functional anomalies correlated with plasma NfL and GFAP, offering exploratory clues for PD-RBD neuropathology and candidate biomarkers requiring further validation.