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From mechanisms to future therapy: a synopsis of isolated REM sleep behavior disorder as early synuclein-related disease
Ambra Stefani, Elena Antelmi, Dario Arnaldi, Isabelle Arnulf, Emmanuel During, Birgit Högl, Michele M. T. Hu, Alex Iranzo et al.. Molecular Neurodegeneration, 2025-02-11
Topic: Brain proteins, microglia and lab models
Plain-language summary
Parkinson disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy are synucleinopathies, characterized by neuronal loss, gliosis and the abnormal deposition of α-synuclein in vulnerable areas of the nervous system. Neurodegeneration begins however several years before clinical onset of motor, cognitive or autonomic symptoms. The isolated form of REM sleep behavior disorder (RBD), a parasomnia with dream enactment behaviors and excessive muscle activity during REM sleep, is an early stage synucleinopathy. The neurophysiological hallmark of RBD is REM sleep without atonia (RWSA), i.e. the loss of physiological muscle atonia during REM sleep. RBD pathophysiology is not fully clarified yet, but clinical and basic science suggest that ɑ-syn pathology begins in the lower brainstem where REM atonia circuits are located, including the sublaterodorsal tegmental/subcoeruleus nucleus and the ventral medulla, then propagates rostrally to brain regions such as the substantia nigra, limbic system, cortex. Genetically, there is only a partial overlap between RBD, PD and DLB, and individuals with iRBD may represent a specific subpopulation. A genome-wide association study identified five loci, which all seem to revolve around the GBA1 pathway. iRBD patients often show subtle motor, cognitive, autonomic and/or sensory signs, neuroimaging alterations as well as biofluid and tissue markers of neurodegeneration (in particular pathologic α-synuclein aggregates), which can be useful for risk stratification. Patients with iRBD represent thus the ideal population for neuroprotective/neuromodulating trials. This review provides insights into these aspects, highlighting and substantiating the central role of iRBD in treatment development strategies for synucleinopathies.
What this study adds
Evidence grade: Low
This review describes isolated REM sleep behavior disorder as an early stage of synuclein-related disease such as Parkinson's disease and dementia with Lewy bodies, with alpha-synuclein pathology likely starting in the lower brainstem. It discusses mechanisms and future therapy directions, but no treatment or cure is established.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Stefani, A., Antelmi, E., Arnaldi, D., Arnulf, I., During, E., Högl, B., et al. (2025). From mechanisms to future therapy: a synopsis of isolated REM sleep behavior disorder as early synuclein-related disease. Molecular Neurodegeneration. https://doi.org/10.1186/s13024-025-00809-0
Vancouver
Stefani A, Antelmi E, Arnaldi D, Arnulf I, During E, Högl B, et al. From mechanisms to future therapy: a synopsis of isolated REM sleep behavior disorder as early synuclein-related disease. Molecular Neurodegeneration. 2025. doi:10.1186/s13024-025-00809-0. PMID: 39934903.
BibTeX
@article{stefani2025-39934903,
author = {Stefani, Ambra and Antelmi, Elena and Arnaldi, Dario and Arnulf, Isabelle and During, Emmanuel and Högl, Birgit and Hu, Michele M. T. and Iranzo, Alex and others},
title = {{From mechanisms to future therapy: a synopsis of isolated REM sleep behavior disorder as early synuclein-related disease}},
journal = {Molecular Neurodegeneration},
year = {2025},
doi = {10.1186/s13024-025-00809-0},
pmid = {39934903},
url = {https://doi.org/10.1186/s13024-025-00809-0}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- RBD pathophysiology is not fully clarified yet, but clinical and basic science suggest that ɑ-syn pathology begins in the lower brainstem where REM atonia circuits are located, including the sublaterodorsal tegmental/subcoeruleus nucleus and the ventral medulla, then propagates rostrally to brain regions such as the substantia nigra, limbic system, cortex.
Why it matters
This review describes isolated REM sleep behavior disorder as an early stage of synuclein-related disease such as Parkinson's disease and dementia with Lewy bodies, with alpha-synuclein pathology likely starting in the lower brainstem. It discusses mechanisms and future therapy directions, but no treatment or cure is established.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular Neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 46 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 25.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ziv Gan‐Or: h-index 62 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 18 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39934903) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-025-00809-0
- PubMed: 39934903
- Original source →
- Free full text: Molecular Neurodegeneration →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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