REM-Sleep Behavior Disorder: An Early Window Into Synucleinopathies
A recent news article from Sleep Review highlights the growing recognition of REM Sleep Behavior Disorder (RBD) as an important early clinical indicator associated with synucleinopathies.
RBD is commonly characterized by its most immediate and harmful symptom, described as dream enactment behaviors. While the underlying neurological root of RBD is unknown to-date, symptoms are caused by the loss of normal muscle paralysis during REM sleep.1 Increasingly, research suggests that isolated RBD may represent one of the earliest clinical manifestations of underlying synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Some research has also begun to explore the potential value of specific biomarkers and physiological expressions of RBD that may be able to track progression and predict phenoconversion to any synucleinopathy.2
The article discusses advances in the availability of minimally invasive biomarkers are helping clinicians better understand and evaluate patients who may be at risk for neurodegenerative disease progression. The authors highlight that an emerging approach is the use of skin biopsy to detect phosphorylated alpha-synuclein (P-SYN) within cutaneous nerve fibers through the Syn-One Test®.
In patients with RBD, a skin biopsy may help sleep specialists identify underlying synuclein pathology years before motor symptoms appear. This biomarker-supported approach may provide additional clinical insight in patients with suspected synucleinopathy and support more informed diagnostic evaluation. For example, clinicians can use a P-SYN biopsy result to guide interventions and aid in clinical trial patient selection
As interest in prodromal disease detection continues to grow, the intersection of sleep medicine, neurology, and diagnostic innovation is becoming increasingly important. Research surrounding RBD and alpha-synuclein detection continues to advance understanding of the early stages of neurodegenerative disease and the potential role of skin-based biomarkers in clinical practice. CND looks forward to continuing to partner with these fields of research to bring innovation to RBD patients.
References
1Stefani A, Antelmi E, Arnaldi D, et al. From mechanisms to future therapy: a synopsis of isolated REM sleep behavior disorder as early synuclein-related disease. Mol Neurodegener. 2025;20(1):19. Published 2025 Feb 11. doi:10.1186/s13024-025-00809-0
2de Natale ER, Wilson H, Politis M. Predictors of RBD progression and conversion to synucleinopathies. Curr Neurol Neurosci Rep. 2022;22(2):93-104. doi:10.1007/s11910-022-01171-0
