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α-Synuclein Seeding Activity in Fixed Antemortem Skin Biopsies From Patients With Synucleinopathies
Wang Z, Gerasimenko M, Gilliland T, Bellaire B, Levine T, Gibbons C.. Research Square, 2026-10-11
Topic: Plasma and spinal-fluid biomarkers
Abstract α-Synuclein seed amplification assays can detect seed-competent pathological α-synuclein in fresh and frozen biospecimens, but their performance in fixed antemortem skin biopsies is less well defined. We applied an optimized real-time quaking-induced conversion assay to paraformaldehyde-fixed skin biopsy sections from participants with Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and controls. Fixed tissue retained measurable α-synuclein seeding activity, although amplification was delayed and the apparent 50% seeding dose was lower than in unfixed or autopsy skin. In this selected proof-of-concept cohort, SAA positivity was observed in 70% of PD, 80% of DLB, 80% of MSA, and 20% of control samples; exploratory ROC analysis yielded an AUC of 0.86. Seeding readouts correlated with Hoehn and Yahr stage but not significantly with MoCA score or pS129 α-synuclein burden. Fixed skin biopsies can therefore provide complementary morphological and functional measures of peripheral α-synuclein pathology.
Key findings
- Seeding readouts correlated with Hoehn and Yahr stage but not significantly with MoCA score or pS129 α-synuclein burden.
Study details
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 24 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and 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 15 of the 62 points we could judge it on, which is 24 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 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 | — / 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 | 15 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 15 of the 62 points we could judge it on is 24 out of 100. |
| Total | 24 / 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 →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Wang, Z., Gerasimenko, M., Gilliland, T., Bellaire, B., Levine, T., & Gibbons, C. (2026). α-Synuclein Seeding Activity in Fixed Antemortem Skin Biopsies From Patients With Synucleinopathies. Research Square. https://doi.org/10.21203/rs.3.rs-10953905/v1
Vancouver
Wang Z, Gerasimenko M, Gilliland T, Bellaire B, Levine T, Gibbons C. α-Synuclein Seeding Activity in Fixed Antemortem Skin Biopsies From Patients With Synucleinopathies. Research Square. 2026. doi:10.21203/rs.3.rs-10953905/v1.
BibTeX
@article{wang2026-b7f39e6b,
author = {Wang, Z. and Gerasimenko, M. and Gilliland, T. and Bellaire, B. and Levine, T. and Gibbons, C.},
title = {{α-Synuclein Seeding Activity in Fixed Antemortem Skin Biopsies From Patients With Synucleinopathies}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10953905/v1},
url = {https://doi.org/10.21203/rs.3.rs-10953905/v1}
}
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