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Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease
Conway KA, Harper JD, Lansbury PT.. Nature medicine, 1998-11-01
Topic: Brain proteins, microglia and lab models
Two mutations in the gene encoding alpha-synuclein have been linked to early-onset Parkinson's disease (PD). alpha-Synuclein is a component of Lewy bodies, the fibrous cytoplasmic inclusions characteristic of nigral dopaminergic neurons in the PD brain. This connection between genetics and pathology suggests that the alpha-synuclein mutations may promote PD pathogenesis by accelerating Lewy body formation. To test this, we studied alpha-synuclein folding and aggregation in vitro, in the absence of other Lewy body-associated molecules. We demonstrate here that both mutant forms of alpha-synuclein (A53T and A30P) are, like wild-type alpha-synuclein (WT), disordered in dilute solution. However, at higher concentrations, Lewy body-like fibrils and discrete spherical assemblies are formed; most rapidly by A53T. Thus, mutation-induced acceleration of alpha-synuclein fibril formation may contribute to the early onset of familial PD.
Key findings
- This connection between genetics and pathology suggests that the alpha-synuclein mutations may promote PD pathogenesis by accelerating Lewy body formation.
Why it matters
In test-tube experiments with purified alpha-synuclein, the normal protein and two mutant forms linked to early-onset familial Parkinson's disease (A53T and A30P) were all unstructured when dilute, but at higher concentrations formed Lewy body-like fibrils and spherical clumps, most rapidly with A53T. The authors conclude that faster fibril formation "may contribute" to the early onset of familial Parkinson's disease. This is protein chemistry, not a study of patients, and it is not about Alzheimer's or any treatment.
Study details
- Evidence strengthLow
How this study scored 58/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (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 | 1 / 5 | 1998 — older than 20 years, still counted |
| 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 | Laboratory or animal study (title names “in vitro”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 1,505 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 50.2 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 5 / 6 | Cited 37.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 3 / 4 | Cited 100 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Peter T. Lansbury: h-index 85 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9809558) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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. Check the citation against the original before you use it.
APA 7th
Conway, K. A., Harper, J. D., & Lansbury, P. T. (1998). Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nature medicine. https://doi.org/10.1038/3311
Vancouver
Conway KA, Harper JD, Lansbury PT. Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nature medicine. 1998. doi:10.1038/3311. PMID: 9809558.
BibTeX
@article{conway1998-9809558,
author = {Conway, K. A. and Harper, J. D. and Lansbury, P. T.},
title = {{Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease}},
journal = {Nature medicine},
year = {1998},
doi = {10.1038/3311},
pmid = {9809558},
url = {https://doi.org/10.1038/3311}
}
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