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Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue
Dhavale DD, Barclay AM, Borcik CG, Basore K, Berthold DA, Gordon IR, Liu J, Milchberg MH et al.. Nature communications, 2024-03-29
Topic: Brain proteins, microglia and lab models
The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.
Key findings
- These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.
Why it matters
This laboratory study determined the atomic structure of alpha-synuclein fibrils from Lewy body dementia tissue, which may aid study of disease mechanisms, imaging agents and therapeutics. It is early structural research and does not test any treatment, cure or prevention in patients.
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Study details
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (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 | 2024 — 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 | 4 / 7 | Cited 73 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.2 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 16.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 71 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Paul T. Kotzbauer: h-index 37 (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 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38553463) |
| 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: 10.1038/s41467-024-46832-5
- PubMed: 38553463
- Original source →
- Free full text: Nature Communications →
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. 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.
APA 7th
Dhavale, D. D., Barclay, A. M., Borcik, C. G., Basore, K., Berthold, D. A., Gordon, I. R., et al. (2024). Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue. Nature communications. https://doi.org/10.1038/s41467-024-46832-5
Vancouver
Dhavale DD, Barclay AM, Borcik CG, Basore K, Berthold DA, Gordon IR, et al. Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue. Nature communications. 2024. doi:10.1038/s41467-024-46832-5. PMID: 38553463.
BibTeX
@article{dhavale2024-38553463,
author = {Dhavale, D. D. and Barclay, A. M. and Borcik, C. G. and Basore, K. and Berthold, D. A. and Gordon, I. R. and Liu, J. and Milchberg, M. H. and others},
title = {{Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue}},
journal = {Nature communications},
year = {2024},
doi = {10.1038/s41467-024-46832-5},
pmid = {38553463},
url = {https://doi.org/10.1038/s41467-024-46832-5}
}
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