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Rapid-Eye-Movement Sleep Behavior Disorder pp 625–637Cite as

REM Sleep Behavior Disorder: The Link Between Synucleinopathies and REM Sleep Circuits

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Abstract

Normal REM sleep is characterized by vivid dreaming, rapid eye movements, and wake-like cortical activity that are accompanied by generalized skeletal muscle paralysis. A defined network of brainstem nuclei control REM sleep motor paralysis, and abnormal control of this network is thought to underlie the excessive and often violent movements in REM sleep behavior disorder (RBD). A major concern associated with RBD is that the majority of patients (80–90%) without identified comorbidities eventually develop some form of synucleinopathy, primarily Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy. This group of diseases is linked to aggregates of the misfolded endogenous protein alpha-synuclein (αSyn). The high level of association between RBD and later synucleinopathy has led to the hypothesis that RBD itself is an early symptom of developing synucleinopathies that arise from degeneration of the brainstem circuitry that normally suppresses muscle activity in REM sleep. Indeed, animal models show that the integrity of this region is required for normal muscle paralysis across species, and human synucleinopathy patients display αSyn aggregates and signs of degeneration within the brainstem REM sleep network. In this chapter, we outline the clinical and basic science evidence supporting the hypothesis that RBD is caused by synucleinopathy progressing through the brainstem regions that regulate muscle paralysis in normal REM sleep. Understanding RBD progression is vital as it could lead to neuroprotective strategies against later synucleinopathy development.

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  1. Department of Cell and Systems Biology, Centre for Biological Timing and Cognition, University of Toronto, Toronto, ON, Canada

    Dillon McKenna & John Peever

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  1. Minnesota Regional Sleep Disorders Center, Departments of Psychiatry, University of Minnesota Medical School and Hennepin County Medical Center, Minneapolis, MN, USA

    Carlos H. Schenck

  2. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

    Birgit Högl

  3. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Aleksandar Videnovic

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McKenna, D., Peever, J. (2019). REM Sleep Behavior Disorder: The Link Between Synucleinopathies and REM Sleep Circuits. In: Schenck, C., Högl, B., Videnovic, A. (eds) Rapid-Eye-Movement Sleep Behavior Disorder. Springer, Cham. https://doi.org/10.1007/978-3-319-90152-7_43

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