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Alpha-synuclein seeding amplification assays in Lewy body dementia: a brief review
Maria Esperanza Bregendahl, Zeynep Bengisu Kaya, Wolfgang Singer, Pamela J. McLean. Molecular Neurodegeneration, 2025-07-01
Topic: Brain proteins, microglia and lab models
Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is characterized by cognitive decline, sleep disturbances, motor dysfunction, and other debilitating clinical symptoms. Neuropathologically, LBD is characterized by the progressive accumulation of alpha-synuclein (aSYN) in vulnerable cellular populations in the brain. Diagnosing LBD is challenging due to the overlap of clinical symptoms with Alzheimer's disease (AD) and other neurodegenerative disorders with current diagnostic tools, including clinical examinations by specialized neurologists and brain imaging, limited by accessibility. Taken together, LBD is often misdiagnosed, especially at early disease stages. Seed amplification assays to detect pathogenic aSYN (aSYN SAAs) are emerging as promising tools to detect aSYN pathology in biological specimens. These assays amplify trace amounts of misfolded aSYN, enabling their potential detection in brain, CSF, saliva, skin, and blood. This review compares the sensitivity and specificity of aSYN SAAs across different biological samples and explores the potential of the assay as a diagnostic in LBD. We also highlight challenges that will need to be addressed going forward if the aSYN SAA is to be widely adopted as a diagnostic test. Despite current limitations, aSYN SAAs hold promise for early and precise diagnosis, paving the way for targeted treatments that could significantly improve patient care and outcomes.
Key findings
- Taken together, LBD is often misdiagnosed, especially at early disease stages.
- Despite current limitations, aSYN SAAs hold promise for early and precise diagnosis, paving the way for targeted treatments that could significantly improve patient care and outcomes.
Why it matters
This review states that alpha-synuclein seeding amplification assays hold promise for early and precise diagnosis of Lewy body dementia, which is often misdiagnosed. However, current limitations need to be addressed before the assay can be widely adopted as a diagnostic test.
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Study details
- Evidence strengthLow
How this study scored 43/100
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 (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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 12 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 6.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 12 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pamela J. McLean: h-index 63 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40598304) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-025-00868-3
- PubMed: 40598304
- 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).
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. Check the citation against the original before you use it.
APA 7th
Bregendahl, M. E., Kaya, Z. B., Singer, W., & McLean, P. J. (2025). Alpha-synuclein seeding amplification assays in Lewy body dementia: a brief review. Molecular Neurodegeneration. https://doi.org/10.1186/s13024-025-00868-3
Vancouver
Bregendahl ME, Kaya ZB, Singer W, McLean PJ. Alpha-synuclein seeding amplification assays in Lewy body dementia: a brief review. Molecular Neurodegeneration. 2025. doi:10.1186/s13024-025-00868-3. PMID: 40598304.
BibTeX
@article{bregendahl2025-40598304,
author = {Bregendahl, Maria Esperanza and Kaya, Zeynep Bengisu and Singer, Wolfgang and McLean, Pamela J.},
title = {{Alpha-synuclein seeding amplification assays in Lewy body dementia: a brief review}},
journal = {Molecular Neurodegeneration},
year = {2025},
doi = {10.1186/s13024-025-00868-3},
pmid = {40598304},
url = {https://doi.org/10.1186/s13024-025-00868-3}
}
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