Home › Research › Biomarkers
Cerebrospinal fluid α-synuclein seed amplification assay positivity identifies a prognostically distinct subgroup in amyotrophic lateral sclerosis
Obara K, Mastrangelo A, Ranieri A, Janelidze S, Ito D, Yamamoto M, Vacchiano V, Liguori R et al.. medRxiv, 2026-10-26
Topic: Plasma and spinal-fluid biomarkers
Results Strong αSyn SAA positivity was detected in 24/443 patients with ALS (5.4%); overall positivity, including weak-positive samples, was 37/443 (8.4%). Patients with ALS did not have significantly higher odds of SAA positivity than Aβ-negative CU participants (age– and sex-adjusted odds ratio [OR] 1.33, 95% CI [0.82, 2.14]) and had significantly lower odds than patients with Alzheimer’s disease dementia (OR 0.44, [0.27, 0.70]). Among patients with sporadic ALS, strong αSyn SAA positivity was associated with shorter tracheostomy-free survival after adjustment for established predictors including NfL (adjusted HR 2.08 [1.25, 3.45]), whereas weak positivity showed no clear survival association. These findings persisted in analyses including familial or genetic ALS cases and in those restricted to Aβ-negative patients. These findings provide ante-mortem evidence that α-synuclein co-pathology may contribute to prognostic heterogeneity in ALS.
Key findings
- Results Strong αSyn SAA positivity was detected in 24/443 patients with ALS (5.4%); overall positivity, including weak-positive samples, was 37/443 (8.4%).
- Patients with ALS did not have significantly higher odds of SAA positivity than Aβ-negative CU participants (age– and sex-adjusted odds ratio [OR] 1.33, 95% CI [0.82, 2.14]) and had significantly lower odds than patients with Alzheimer’s disease dementia (OR 0.44, [0.27, 0.70]).
- Among patients with sporadic ALS, strong αSyn SAA positivity was associated with shorter tracheostomy-free survival after adjustment for established predictors including NfL (adjusted HR 2.08 [1.25, 3.45]), whereas weak positivity showed no clear survival association.
- These findings persisted in analyses including familial or genetic ALS cases and in those restricted to Aβ-negative patients.
- These findings provide ante-mortem evidence that α-synuclein co-pathology may contribute to prognostic heterogeneity in ALS.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designlongitudinal study
- Participants248
- Effect size5.4%; 8.4%; OR 0.44
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 48 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for randomised / blinded because the record does not state it. We have no data on 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 and multi-centre collaboration, so those were left out: it earned 30 of the 62 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 248 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 30 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 30 of the 62 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Obara, K., Mastrangelo, A., Ranieri, A., Janelidze, S., Ito, D., Yamamoto, M., et al. (2026). Cerebrospinal fluid α-synuclein seed amplification assay positivity identifies a prognostically distinct subgroup in amyotrophic lateral sclerosis. medRxiv. https://doi.org/10.64898/2026.10.23.26366349
Vancouver
Obara K, Mastrangelo A, Ranieri A, Janelidze S, Ito D, Yamamoto M, et al. Cerebrospinal fluid α-synuclein seed amplification assay positivity identifies a prognostically distinct subgroup in amyotrophic lateral sclerosis. medRxiv. 2026. doi:10.64898/2026.10.23.26366349.
BibTeX
@article{obara2026-0d68a0e1,
author = {Obara, K. and Mastrangelo, A. and Ranieri, A. and Janelidze, S. and Ito, D. and Yamamoto, M. and Vacchiano, V. and Liguori, R. and others},
title = {{Cerebrospinal fluid α-synuclein seed amplification assay positivity identifies a prognostically distinct subgroup in amyotrophic lateral sclerosis}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.23.26366349},
url = {https://doi.org/10.64898/2026.10.23.26366349}
}