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Plasma NfL, GFAP, and pTau181 in patients with isolated REM sleep behavior disorder
Claudio Liguori, Mariana Fernandes, Cinzia Zatti, Matteo Carpi, Chiara Tolassi, Greta Testone, Flavia Cirillo, Matteo Antonucci et al.. Sleep, 2025-12-11
Topic: Plasma and spinal-fluid biomarkers
The study included 44 iRBD patients (81.8% males, mean age 71.0 ± 6.4 years), 55 HC (66.3% males, mean age 69.1 ± 5.5 years), and 28 AD patients (82.1% males, mean age of 70.4 ± 6.7 years). iRBD patients showed significantly higher plasma NfL and GFAP levels and similar pTau181 levels compared to HC. Compared to AD patients, iRBD patients had lower levels of GFAP, NfL, and pTau181. In iRBD, GFAP and NfL levels were significantly correlated, while no correlations were observed between plasma biomarkers and clinical symptoms. High plasma NfL and GFAP levels in iRBD patients reflect a possible ongoing neurodegenerative process. Normal pTau181 plasma levels in iRBD suggest that AD-related neurodegeneration is not present at this stage. Future studies on plasma markers predicting phenoconversion are crucial for setting neuroprotective interventions in iRBD patients. Statement of Significance This study identifies plasma biomarkers that reflect neurodegeneration in idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of α-synucleinopathies. Higher plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels in iRBD patients compared to healthy controls suggest early neuronal and glial degeneration, while similar phosphorylated-Tau 181 levels indicate an absence of Alzheimer's disease co-pathology. These findings support the utility of NfL and GFAP as potential blood-based markers for tracking early neurodegenerative changes in iRBD. Further studies focusing on these markers in predicting disease progression could be instrumental in guiding timely neuroprotective interventions.
Key findings
- The study included 44 iRBD patients (81.8% males, mean age 71.0 ± 6.4 years), 55 HC (66.3% males, mean age 69.1 ± 5.5 years), and 28 AD patients (82.1% males, mean age of 70.4 ± 6.7 years). iRBD patients showed significantly higher plasma NfL and GFAP levels and similar pTau181 levels compared to HC.
- Compared to AD patients, iRBD patients had lower levels of GFAP, NfL, and pTau181.
- In iRBD, GFAP and NfL levels were significantly correlated, while no correlations were observed between plasma biomarkers and clinical symptoms.
- High plasma NfL and GFAP levels in iRBD patients reflect a possible ongoing neurodegenerative process.
- Normal pTau181 plasma levels in iRBD suggest that AD-related neurodegeneration is not present at this stage.
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Study details
- Study designcross-sectional
- Participants44
- Effect size81.8%; 66.3%; 82.1%
- Evidence strengthLow
How this study scored 61/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 34 of the 56 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Sleep) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 1 / 4 | 44 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40488440) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 34 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 34 of the 56 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Liguori, C., Fernandes, M., Zatti, C., Carpi, M., Tolassi, C., Testone, G., et al. (2025). Plasma NfL, GFAP, and pTau181 in patients with isolated REM sleep behavior disorder. Sleep. https://doi.org/10.1093/sleep/zsaf163
Vancouver
Liguori C, Fernandes M, Zatti C, Carpi M, Tolassi C, Testone G, et al. Plasma NfL, GFAP, and pTau181 in patients with isolated REM sleep behavior disorder. Sleep. 2025. doi:10.1093/sleep/zsaf163. PMID: 40488440.
BibTeX
@article{liguori2025-40488440,
author = {Liguori, Claudio and Fernandes, Mariana and Zatti, Cinzia and Carpi, Matteo and Tolassi, Chiara and Testone, Greta and Cirillo, Flavia and Antonucci, Matteo and others},
title = {{Plasma NfL, GFAP, and pTau181 in patients with isolated REM sleep behavior disorder}},
journal = {Sleep},
year = {2025},
doi = {10.1093/sleep/zsaf163},
pmid = {40488440},
url = {https://doi.org/10.1093/sleep/zsaf163}
}
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