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Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy
Shahnawaz M, Mukherjee A, Pritzkow S, Mendez N, Rabadia P, Liu X, Hu B, Schmeichel A et al.. Nature, 2020-02-05
Topic: Brain proteins, microglia and lab models
Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of α-synuclein, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy 1 . Clinically, it is challenging to differentiate Parkinson's disease and multiple system atrophy, especially at the early stages of disease 2 . Aggregates of α-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of α-synuclein that can self-propagate and spread from cell to cell 3-6 . Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect α-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity 7,8 . Here we show that the α-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson's disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of α-synuclein-PMCA, and found that the characteristics of the α-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson's disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that α-synuclein aggregates that are associated with Parkinson's disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of α-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson's disease and multiple system atrophy.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Shahnawaz, M., Mukherjee, A., Pritzkow, S., Mendez, N., Rabadia, P., Liu, X., et al. (2020). Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy. Nature. https://doi.org/10.1038/s41586-020-1984-7
Vancouver
Shahnawaz M, Mukherjee A, Pritzkow S, Mendez N, Rabadia P, Liu X, et al. Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy. Nature. 2020. doi:10.1038/s41586-020-1984-7. PMID: 32025029.
BibTeX
@article{shahnawaz2020-32025029,
author = {Shahnawaz, M. and Mukherjee, A. and Pritzkow, S. and Mendez, N. and Rabadia, P. and Liu, X. and Hu, B. and Schmeichel, A. and others},
title = {{Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy}},
journal = {Nature},
year = {2020},
doi = {10.1038/s41586-020-1984-7},
pmid = {32025029},
url = {https://doi.org/10.1038/s41586-020-1984-7}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of α-synuclein, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy 1 .
- Here we show that the α-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson's disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%.
- These findings suggest that α-synuclein aggregates that are associated with Parkinson's disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA.
- Our results may help to improve our understanding of the mechanism of α-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson's disease and multiple system atrophy.
Why it matters
This laboratory study showed that an assay measuring α-synuclein aggregates in cerebrospinal fluid could tell Parkinson's disease apart from multiple system atrophy with high sensitivity. It concerns diagnosis of these synucleinopathies, not treatment, cure or prevention of Alzheimer's disease.
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Study details
- Effect size95.4%
- Evidence strengthLow
How this study scored 61/100
Published in a top-tier journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (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 | 2020 — 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 826 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 103.2 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 6 / 6 | Cited 42.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 4 / 4 | Cited 368 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Claudio A. Soto: h-index 90 (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 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32025029) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 61 / 100 | — |
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