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Review
. 2025 Oct 24;25(1):73.
doi: 10.1007/s11910-025-01452-4.

REM Sleep Behavior Disorder as a Prodromal Synucleinopathy: Updates on Clinical and Laboratory Biomarkers, and Implications for Neuroprotective Trials

Lee E Neilson  1   2   3   4 , Youssef I Khattab  5 , Miranda M Lim  6   7   5
Affiliations
Review

REM Sleep Behavior Disorder as a Prodromal Synucleinopathy: Updates on Clinical and Laboratory Biomarkers, and Implications for Neuroprotective Trials

Lee E Neilson et al. Curr Neurol Neurosci Rep. .

Abstract

Purpose of review: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia notable for its association with the later development of diseases with pathological α-synuclein deposition, including Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). The goal of this review is to summarize the recent advances in characterizing the clinical deficits, neuroimaging characteristics, and biomarker assay development of individuals with RBD.

Recent findings: Clinical research indicates that many people with RBD are presenting to clinical attention for reasons other than dream enactment behavior. They experience deficits in neuropsychiatric, autonomic, and motor domains and co-presentation of these features with RBD predict a faster rate of phenoconversion to PD, DLB, or MSA. RBD is considered a prodromal synucleinopathy with early abnormalities in α-synuclein protein pathways, together with inflammation and mitochondrial dysfunction being recognized as key pathophysiological mechanisms. Seed amplification assays for α-synuclein in various tissue types hold tremendous promise for antemortem diagnosis. RBD is clearly an at-risk population for neurodegenerative disease with well-defined measures that can refine enrollment and better target prodromal populations for interventional clinical trials. The first neuroprotective trials are underway.

Keywords: Neuroprotection; Parkinson’s disease; Phenoconversion; Prodromal synucleinopathy; REM sleep behavior disorder.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors.

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