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Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC
Groveman BR, Orrù CD, Hughson AG, Raymond LD, Zanusso G, Ghetti B, Campbell KJ, Safar J et al.. Acta neuropathologica communications, 2018-02-09
Topic: Brain proteins, microglia and lab models
The diagnosis and treatment of synucleinopathies such as Parkinson disease and dementia with Lewy bodies would be aided by the availability of assays for the pathogenic disease-associated forms of α-synuclein (αSyn D ) that are sufficiently sensitive, specific, and practical for analysis of accessible diagnostic specimens. Two recent αSyn D seed amplification tests have provided the first prototypes for ultrasensitive and specific detection of αSyn D in patients' cerebrospinal fluid. These prototypic assays require 5-13 days to perform. Here, we describe an improved α-synuclein real time quaking-induced conversion (αSyn RT-QuIC) assay that has similar sensitivity and specificity to the prior assays, but can be performed in 1-2 days with quantitation. Blinded analysis of cerebrospinal fluid from 29 synucleinopathy cases [12 Parkinson's and 17 dementia with Lewy bodies] and 31 non-synucleinopathy controls, including 16 Alzheimer's cases, yielded 93% diagnostic sensitivity and 100% specificity for this test so far. End-point dilution analyses allowed quantitation of relative amounts of αSyn D seeding activity in cerebrospinal fluid samples, and detection in as little as 0.2 μL. These results confirm that αSyn D seeding activity is present in cerebrospinal fluid. We also demonstrate that it can be rapidly detected, and quantitated, even in early symptomatic stages of synucleinopathy.
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APA 7th
Groveman, B. R., Orrù, C. D., Hughson, A. G., Raymond, L. D., Zanusso, G., Ghetti, B., et al. (2018). Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC. Acta neuropathologica communications. https://doi.org/10.1186/s40478-018-0508-2
Vancouver
Groveman BR, Orrù CD, Hughson AG, Raymond LD, Zanusso G, Ghetti B, et al. Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC. Acta neuropathologica communications. 2018. doi:10.1186/s40478-018-0508-2. PMID: 29422107.
BibTeX
@article{groveman2018-29422107,
author = {Groveman, B. R. and Orrù, C. D. and Hughson, A. G. and Raymond, L. D. and Zanusso, G. and Ghetti, B. and Campbell, K. J. and Safar, J. and others},
title = {{Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC}},
journal = {Acta neuropathologica communications},
year = {2018},
doi = {10.1186/s40478-018-0508-2},
pmid = {29422107},
url = {https://doi.org/10.1186/s40478-018-0508-2}
}
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Key findings
- These results confirm that αSyn D seeding activity is present in cerebrospinal fluid.
Why it matters
This study describes an improved laboratory test that detects disease-associated alpha-synuclein seeds in cerebrospinal fluid in 1-2 days, with 93% sensitivity and 100% specificity in the samples tested so far. It is a diagnostic test for synucleinopathies such as Parkinson's disease and dementia with Lewy bodies, not a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 54/100
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 (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (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 | 2 / 5 | 2018 — within 10 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 | 6 / 7 | Cited 422 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 42.2 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 5 / 6 | Cited 22.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 3 / 4 | Cited 168 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Byron W. Caughey: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29422107) |
| Free to read | 2 / 2 | Free to read |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40478-018-0508-2
- PubMed: 29422107
- Original source →
- Free full text: Acta Neuropathologica Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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