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

Lee E. Neilson; Youssef I. Khattab; Miranda M. Lim

doi:10.1007/s11910-025-01452-4

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

Journal article

Peer reviewed

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

Lee E. Neilson, Youssef I. Khattab and Miranda M. Lim

Current neurology and neuroscience reports, Vol.25(1), p.73

10/24/2025

DOI: 10.1007/s11910-025-01452-4

PMCID: PMC12831559

PMID: 41134495

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12831559/View

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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. Summary 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.

Medicine

Medicine & Public Health

Neurology

Neurosciences

Review

Topical Collection on Sleep

Details

Title: Subtitle: REM Sleep Behavior Disorder as a Prodromal Synucleinopathy: Updates on Clinical and Laboratory Biomarkers, and Implications for Neuroprotective Trials
Creators: Lee E. Neilson - VA Portland Health Care System
Youssef I. Khattab - Oregon Health & Science University
Miranda M. Lim - Oregon Health & Science University
Resource Type: Journal article
Publication Details: Current neurology and neuroscience reports, Vol.25(1), p.73
DOI: 10.1007/s11910-025-01452-4
PMID: 41134495
PMCID: PMC12831559
NLM abbreviation: Curr Neurol Neurosci Rep
ISSN: 1528-4042
eISSN: 1534-6293
Publisher: Springer US
Grant note: CX00253 / VA CSR&D
Language: English
Date published: 10/24/2025
Academic Unit: Neurology
Record Identifier: 9985089125102771

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