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Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder
Aline Delva, Amélie Pelletier, Emma N. Somerville, Jacques Yves Montplaisir, Jean‐François Gagnon, Gwendlyn Kollmorgen, Tony Kam‐Thong, Thomas Kustermann et al.. Brain, 2025-01-02
Topic: Brain proteins, microglia and lab models
Blood-based biomarkers for Alzheimer's disease (AD) pathology have been investigated intensively as markers for AD-related neurodegeneration. Comorbid AD pathology is common in dementia with Lewy bodies (DLB). Accordingly, we hypothesized that plasma biomarkers associated with AD pathology might be useful to predict DLB in a cohort of idiopathic/isolated REM sleep behaviour disorder (iRBD), an incipient synucleinopathy. The aim of this study was to determine whether plasma amyloid-β and pTau181 biomarkers can predict DLB. This longitudinal single-centre (Canada) cohort study included 158 individuals with polysomnography-confirmed iRBD between September 2004 and October 2022, each providing blood plasma samples, who were then offered prospective follow-up. Plasma Aβ40, Aβ42 and pTau181 levels were measured using NeuroToolKit, a prototype assay panel of neurodegeneration (Roche Diagnostics International Ltd). The primary outcome was the association between plasma biomarkers at baseline and eventual development of DLB. Correlations between plasma markers and baseline cognitive tests were assessed. A total of 142 iRBD participants [109 male (77%); mean ± SD, 67.6 ± 8.0 years of age] were included in the final analysis. On prospective follow-up (2.9 ± 2.1 years after sampling), 32 individuals phenoconverted to a defined neurodegenerative syndrome (18 DLB, 13 Parkinson's disease and one multiple system atrophy). The combined phenoconvertor group had lower baseline plasma Aβ42/40 ratio compared with non-phenoconvertors (mean ± SD, 0.103 ± 0.010 versus 0.114 ± 0.012, P < 0.001) and higher pTau181 levels (0.993 ± 0.354 versus 0.784 ± 0.266 pg/ml, P = 0.008). When divided by phenoconversion subtype, significant differences were seen selectively in DLB convertors [Aβ42/40 = 0.101 ± 0.010, difference -0.011, 95% confidence interval (-0.016; -0.005), P < 0.001; pTau181 = 1.144 ± 0.326 pg/ml, difference 0.282 pg/ml, 95% confidence interval (0.146; 0.418), P < 0.001]. Cross-sectional analysis showed that plasma pTau181 (but not Aβ42/40) was correlated with cognitive tests across various domains. Our results indicate that plasma Aβ42/40 ratio and pTau181 can predict conversion to DLB in iRBD.
Key findings
- Accordingly, we hypothesized that plasma biomarkers associated with AD pathology might be useful to predict DLB in a cohort of idiopathic/isolated REM sleep behaviour disorder (iRBD), an incipient synucleinopathy.
- The combined phenoconvertor group had lower baseline plasma Aβ42/40 ratio compared with non-phenoconvertors (mean ± SD, 0.103 ± 0.010 versus 0.114 ± 0.012, P < 0.001) and higher pTau181 levels (0.993 ± 0.354 versus 0.784 ± 0.266 pg/ml, P = 0.008).
- When divided by phenoconversion subtype, significant differences were seen selectively in DLB convertors [Aβ42/40 = 0.101 ± 0.010, difference -0.011, 95% confidence interval (-0.016; -0.005), P < 0.001; pTau181 = 1.144 ± 0.326 pg/ml, difference 0.282 pg/ml, 95% confidence interval (0.146; 0.418), P < 0.001].
- Cross-sectional analysis showed that plasma pTau181 (but not Aβ42/40) was correlated with cognitive tests across various domains.
- Our results indicate that plasma Aβ42/40 ratio and pTau181 can predict conversion to DLB in iRBD.
Why it matters
In people with idiopathic REM sleep behaviour disorder, lower baseline plasma Aβ42/40 ratio and higher pTau181 levels were found in those who later developed a neurodegenerative syndrome including dementia with Lewy bodies. This suggests blood markers may help predict conversion, but the study was a single-centre cohort and did not test any treatment.
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Study details
- Study designcohort study
- Participants158
- Evidence strengthModerate
How this study scored 65/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 2 / 4 | 158 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | 3 / 7 | Cited 26 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 16.5× 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 26 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ronald B. Postuma: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | McGill University: institution h-index 1,373 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39761530) |
| Free to read | 2 / 2 | Free to read |
| Total | 65 / 100 | — |
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Read the original
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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
Delva, A., Pelletier, A., Somerville, E. N., Montplaisir, J. Y., Gagnon, J., Kollmorgen, G., et al. (2025). Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder. Brain. https://doi.org/10.1093/brain/awaf003
Vancouver
Delva A, Pelletier A, Somerville EN, Montplaisir JY, Gagnon J, Kollmorgen G, et al. Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder. Brain. 2025. doi:10.1093/brain/awaf003. PMID: 39761530.
BibTeX
@article{delva2025-39761530,
author = {Delva, Aline and Pelletier, Amélie and Somerville, Emma N. and Montplaisir, Jacques Yves and Gagnon, Jean‐François and Kollmorgen, Gwendlyn and Kam‐Thong, Tony and Kustermann, Thomas and others},
title = {{Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder}},
journal = {Brain},
year = {2025},
doi = {10.1093/brain/awaf003},
pmid = {39761530},
url = {https://doi.org/10.1093/brain/awaf003}
}
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