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A modified α-synuclein seed amplification assay in Lewy body dementia using Raman spectroscopy and machine learning analysis
Nathan P. Coles, Suzan Elsheikh, Alaa Gouda, Agathe Quesnel, Lucy Butler, Ojodomo J. Achadu, Meez Islam, Karunakaran Kalesh et al.. Journal of Neuroscience Methods, 2025-11-15
Topic: Brain proteins, microglia and lab models
Lewy body dementias (LBD), comprising dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), are defined by misfolded α-synuclein aggregation. Seed amplification assays (SAAs), such as RT-QuIC, enable sensitive detection of α-synuclein aggregates but typically provide binary readouts and require fluorescence labeling. Raman spectroscopy offers a label-free approach to detect subtle biochemical changes, and its diagnostic potential can be enhanced with machine learning. This proof-of-concept study aimed to evaluate whether Raman spectroscopy combined with machine learning can improve SAA-based discrimination of LBD from controls in cerebrospinal fluid (CSF). We analyzed a small number of post-mortem CSF samples from pathologically confirmed DLB (n = 2), PDD (n = 2), and controls (n = 2) using a 7-day SAA. Raman spectra were collected on Days 1, 4, and 7 and analyzed using principal component analysis (PCA) and uniform manifold approximation and projection (UMAP). Following SAA, both PCA and UMAP distinguished combined LBD samples from controls within 24 h (Day 1), reflecting biochemical changes consistent with α-synuclein fibrillation. Spectral shifts indicated decreased α-helical content with increased β-sheet structures. No consistent separation between DLB and PDD was observed. This preliminary study demonstrates that combining Raman spectroscopy with machine learning can enable rapid, label-free detection of disease-specific changes. Despite the very limited sample size, these findings highlight the potential of this novel workflow and strongly warrant its validation in larger cohorts. Schematic overview of the modified SAA process. Monomeric recombinant α-synuclein was incubated with patient CSF and glass beads, before 7-day mechanical agitation. In disease patients, oligomeric α-synuclein recruits monomeric α-synuclein into growing fibrillar chains, which in turn are fragmented through mechanical agitation. These fragments form initial seeds, which elongate further, amplifying α-synuclein signals under Raman spectroscopy. • Raman spectroscopy detects α-synuclein aggregation after seed amplification. • Machine learning distinguishes Lewy body dementia from controls in 24 h. • Label-free assay shows early α-helix to β-sheet structural transitions. • Potential rapid diagnostic tool for synucleinopathies.
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APA 7th
Coles, N. P., Elsheikh, S., Gouda, A., Quesnel, A., Butler, L., Achadu, O. J., et al. (2025). A modified α-synuclein seed amplification assay in Lewy body dementia using Raman spectroscopy and machine learning analysis. Journal of Neuroscience Methods. https://doi.org/10.1016/j.jneumeth.2025.110617
Vancouver
Coles NP, Elsheikh S, Gouda A, Quesnel A, Butler L, Achadu OJ, et al. A modified α-synuclein seed amplification assay in Lewy body dementia using Raman spectroscopy and machine learning analysis. Journal of Neuroscience Methods. 2025. doi:10.1016/j.jneumeth.2025.110617. PMID: 41238048.
BibTeX
@article{coles2025-41238048,
author = {Coles, Nathan P. and Elsheikh, Suzan and Gouda, Alaa and Quesnel, Agathe and Butler, Lucy and Achadu, Ojodomo J. and Islam, Meez and Kalesh, Karunakaran and others},
title = {{A modified α-synuclein seed amplification assay in Lewy body dementia using Raman spectroscopy and machine learning analysis}},
journal = {Journal of Neuroscience Methods},
year = {2025},
doi = {10.1016/j.jneumeth.2025.110617},
pmid = {41238048},
url = {https://doi.org/10.1016/j.jneumeth.2025.110617}
}
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Key findings
- Despite the very limited sample size, these findings highlight the potential of this novel workflow and strongly warrant its validation in larger cohorts.
Why it matters
In a very small proof-of-concept study using post-mortem cerebrospinal fluid from only six people, Raman spectroscopy combined with machine learning distinguished Lewy body dementia samples from controls within 24 hours. The authors state the sample size was very limited and the workflow strongly warrants validation in larger cohorts.
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Study details
- Evidence strengthLow
How this study scored 36/100
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 (Journal of Neuroscience Methods) |
| Journal's citation record | 2 / 4 | Journal of Neuroscience Methods: journal h-index 227 (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 | 1 / 6 | Cited 0.7× 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 Ahmad Adam Khundakar: h-index 22 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Göttingen: institution h-index 934 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41238048) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 100 | — |
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Read the original
- DOI: 10.1016/j.jneumeth.2025.110617
- PubMed: 41238048
- Original source →
- Free full text: Journal of Neuroscience Methods →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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