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α‐Synuclein seed amplification assay in Lewy body dementia versus Alzheimer's disease
Oskar Hoffmann McWilliam, Remarh Bsoul, Eva Løbner Lund, Gunhild Waldemar, Steen Gregers Hasselbalch, Anja Hviid Simonsen, Marie Bruun, Christian von Buchwald et al.. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, 2025-10-01
Topic: Amyloid, tau and blood-test diagnosis
The accuracy of α-synuclein-SAA for DLB was 87% (95% confidence interval [CI]: 77% to 98%) in CSF, 85% (95% CI: 75% to 98%) in skin, 58% (95% CI: 47% to 69%) in olfactory mucosa, and 59% (95% CI: 51% to 66%) in urine. The core symptoms - fluctuations, REM sleep behavior disorder, and parkinsonism - had accuracies for SAA positivity of ≥79%. Notably, 95% of SAA-positive patients also had hyposmia. These findings support the use of CSF and skin α-synuclein-SAAs as diagnostic tools for DLB, with strong associations between SAA and clinical phenotype. In particular, intact olfactory function is associated with a lower risk of SAA positivity. Highlights: CSF and skin biopsies show high diagnostic accuracy for α-synuclein, demonstrating good concordance.Strong correlations exist between core symptoms of DLB and pathological α-synuclein.A very high sensitivity of hyposmia for pathological α-synuclein is observed.A novel proof-of-concept is offered for the potential detection of pathological α-synuclein in urine, marking the first such comparative analysis between patients with DLB and AD.
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APA 7th
McWilliam, O. H., Bsoul, R., Lund, E. L., Waldemar, G., Hasselbalch, S. G., Simonsen, A. H., et al. (2025). α‐Synuclein seed amplification assay in Lewy body dementia versus Alzheimer's disease. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring. https://doi.org/10.1002/dad2.70203
Vancouver
McWilliam OH, Bsoul R, Lund EL, Waldemar G, Hasselbalch SG, Simonsen AH, et al. α‐Synuclein seed amplification assay in Lewy body dementia versus Alzheimer's disease. Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring. 2025. doi:10.1002/dad2.70203. PMID: 41211301.
BibTeX
@article{mcwilliam2025-41211301,
author = {McWilliam, Oskar Hoffmann and Bsoul, Remarh and Lund, Eva Løbner and Waldemar, Gunhild and Hasselbalch, Steen Gregers and Simonsen, Anja Hviid and Bruun, Marie and von Buchwald, Christian and others},
title = {{α‐Synuclein seed amplification assay in Lewy body dementia versus Alzheimer's disease}},
journal = {Alzheimer s \& Dementia Diagnosis Assessment \& Disease Monitoring},
year = {2025},
doi = {10.1002/dad2.70203},
pmid = {41211301},
url = {https://doi.org/10.1002/dad2.70203}
}
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Key findings
- The accuracy of α-synuclein-SAA for DLB was 87% (95% confidence interval [CI]: 77% to 98%) in CSF, 85% (95% CI: 75% to 98%) in skin, 58% (95% CI: 47% to 69%) in olfactory mucosa, and 59% (95% CI: 51% to 66%) in urine.
- The core symptoms - fluctuations, REM sleep behavior disorder, and parkinsonism - had accuracies for SAA positivity of ≥79%.
- Notably, 95% of SAA-positive patients also had hyposmia.
- These findings support the use of CSF and skin α-synuclein-SAAs as diagnostic tools for DLB, with strong associations between SAA and clinical phenotype.
- In particular, intact olfactory function is associated with a lower risk of SAA positivity.
Why it matters
The α-synuclein seed amplification assay showed high accuracy in cerebrospinal fluid and skin for diagnosing dementia with Lewy bodies. This is a diagnostic tool and does not treat, cure, or prevent Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 34/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring) |
| Journal's citation record | 1 / 4 | Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring: journal h-index 86 (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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Kristian Steen Frederiksen: h-index 37 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Copenhagen: institution h-index 1,378 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41211301) |
| Free to read | 2 / 2 | Free to read |
| Total | 34 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/dad2.70203
- PubMed: 41211301
- Original source →
- Free full text: Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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