Supplementary Material for: Plasma BDNF levels, BDNF Val66Met polymorphism, and their association with phenoconversion in isolated REM sleep behavior disorder

Introduction: Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson’s disease (PD). However, no study has investigated peripheral BDNF levels and BDNF Val66Met polymorphism in the prodromal stage of PD and their relationship with disease conversion. Methods: 120 patients with video-polysomnographically (v-PSG) confirmed iRBD and 120 healthy controls (HCs) were enrolled. Genetic analyses were performed, and plasma levels of BDNF were measured. All patients with iRBD underwent comprehensive clinical testings, and 107 iRBD patients were prospectively followed-up. Results: Plasma BDNF levels were significantly lower in the iRBD group than in HCs (18878.85 pg/ml vs. 24649.85 pg/ml, p = 0.002), but no differences were observed in BDNF Val66Met carrier rates between the two groups. Plasma BDNF levels did not differ significantly between BDNF Val66Met carriers and non-carriers. Notably, higher plasma BDNF levels were associated with an increased risk of short-term disease con-version (Hazard Ratio = 3.418, 95% CI 1.520-7.684, p = 0.003), whereas BDNF Val66Met carrier rates showed no such association. Conclusion: Our findings suggest that plasma BDNF is significantly associated with iRBD and may likely serve as a prognostic biomarker for the development of neurodegenerative dis-ease. However, the BDNF Val66Met polymorphism may not be involved in the path-ogenesis of iRBD as well as phenoconversion in the studied population.