Plasma Markers of Astrocytic and Axonal Integrity in Idiopathic/Isolated REM Sleep Behavior Disorder (iRBD) as Predictors of Dementia with Lewy Bodies

Abstract

Background: Plasma biomarkers of neurodegeneration, astrogliosis, and neuroinflammation have been studied as potential biomarkers in neurodegenerative diseases. This study investigated whether these markers may predict phenoconversion to Parkinson's disease or dementia with Lewy bodies (DLB) in idiopathic/isolated REM sleep behavior disorder (iRBD). Methods: In this longitudinal, single-center, iRBD cohort study (enrolled 2004–2022), plasma glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), neurofilament light chain (NfL), snare-associated protein 25 (SNAP25), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and chitinase 3-like protein (YKL-40) were measured using NeuroToolKit (Roche Diagnostics International Ltd). Associations between baseline plasma biomarkers and eventual development of manifest synucleinopathy during follow-up (up to 11 years) were assessed. Results: A total of 143 iRBD participants (110 male, 67.7 ± 8.0 years) were included. Compared with non-phenoconverters, DLB-converters had higher baseline GFAP (0.115 vs. 0.071 ng/ml, P = 0.002) and NfL (3.55 vs. 2.51 pg/ml, P = 0.010). Baseline levels predicted DLB using non-phenoconverters without mild cognitive impairment as reference with area under the curve (AUC) = 0.79 for GFAP and 0.84 for NfL. Conclusion: Higher plasma GFAP and NfL were associated with increased risk of developing DLB in prodromal synucleinopathies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.