REM Sleep Behavior Disorders and Neurodegeneration

Rapid eye movement sleep behaviour disorder (RBD) is a parasomnia in which the normal muscle paralysis of REM sleep is lost, allowing individuals to enact dreams that may be violent or complex. Over the past two decades it has become clear that idiopathic RBD often heralds neurodegenerative synucleinopathies such as Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy. Pathological studies indicate that alpha-synuclein pathology begins in brainstem nuclei responsible for REM atonia and subsequently propagates to midbrain, limbic and cortical regions. Clinically, patients with RBD may exhibit subtle motor, cognitive or autonomic changes years before overt disease. Diagnosis relies on polysomnography demonstrating REM sleep without atonia, and recent advances in imaging, biofluid biomarkers and genetic profiling have refined risk stratification. As a prodromal marker, RBD offers a crucial window for early intervention trials and for understanding mechanisms of synuclein spread. Moreover, RBD has been recognised in non-synucleinopathies, suggesting broader links between sleep circuitry disruption and neurodegeneration.

Research from Nature Portfolio

A genome-wide association study has identified five genetic loci associated with RBD risk, centred on genes involved in alpha-synuclein processing and lysosomal function. Analysis of expression patterns revealed differential regulation of SNCA-AS1 in distinct brain regions of affected individuals, while colocalisation methods implicated SCARB2 in disease susceptibility. Polygenic risk scores derived from these findings distinguish RBD as a unique subpopulation within alpha-synucleinopathies, highlighting pathways that may underlie the transition from isolated sleep disorder to overt neurodegeneration. These genetic insights pave the way for biomarker development and for targeted trials aimed at delaying or preventing synucleinopathy onset.

REM Sleep Behavior Disorders and Neurodegeneration publication trend

The graph below shows the total number of articles in rem sleep behavior disorders and neurodegeneration across all publications each year (not limited to Nature Index journals).

Technical terms

REM sleep without atonia (RWA): Loss of physiological muscle paralysis during REM sleep, permitting dream enactment behaviours.

Alpha-synucleinopathy: A class of neurodegenerative diseases characterised by abnormal aggregation of the protein alpha-synuclein in neurons and glia.

Polysomnography (PSG): A multi-parameter sleep study recording EEG, EMG and other physiological signals to diagnose sleep disorders.

Idiopathic REM sleep behaviour disorder (iRBD): RBD occurring in the absence of overt neurological disease, often serving as a prodromal marker for synucleinopathies.

References

1. Magnetic susceptibility changes in the brainstem reflect REM sleep without atonia severity in isolated REM sleep behavior disorder. npj Parkinson's Disease (2023).
2. Neurodegenerative Disorder Risk in Idiopathic REM Sleep Behavior Disorder: Study in 174 Patients. PLOS ONE (2014).
3. Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: An Update. Aging and Disease (2020).
4. Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects. Nature Communications (2022).