Home › Research › Lewy body dementia
Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies
Peng C, Gathagan RJ, Covell DJ, Medellin C, Stieber A, Robinson JL, Zhang B, Pitkin RM et al.. Nature, 2018-05-09
Topic: Brain proteins, microglia and lab models
In Lewy body diseases-including Parkinson's disease, without or with dementia, dementia with Lewy bodies, and Alzheimer's disease with Lewy body co-pathology 1 -α-synuclein (α-Syn) aggregates in neurons as Lewy bodies and Lewy neurites 2 . By contrast, in multiple system atrophy α-Syn accumulates mainly in oligodendrocytes as glial cytoplasmic inclusions (GCIs) 3 . Here we report that pathological α-Syn in GCIs and Lewy bodies (GCI-α-Syn and LB-α-Syn, respectively) is conformationally and biologically distinct. GCI-α-Syn forms structures that are more compact and it is about 1,000-fold more potent than LB-α-Syn in seeding α-Syn aggregation, consistent with the highly aggressive nature of multiple system atrophy. GCI-α-Syn and LB-α-Syn show no cell-type preference in seeding α-Syn pathology, which raises the question of why they demonstrate different cell-type distributions in Lewy body disease versus multiple system atrophy. We found that oligodendrocytes but not neurons transform misfolded α-Syn into a GCI-like strain, highlighting the fact that distinct α-Syn strains are generated by different intracellular milieus. Moreover, GCI-α-Syn maintains its high seeding activity when propagated in neurons. Thus, α-Syn strains are determined by both misfolded seeds and intracellular environments.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Peng, C., Gathagan, R. J., Covell, D. J., Medellin, C., Stieber, A., Robinson, J. L., et al. (2018). Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies. Nature. https://doi.org/10.1038/s41586-018-0104-4
Vancouver
Peng C, Gathagan RJ, Covell DJ, Medellin C, Stieber A, Robinson JL, et al. Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies. Nature. 2018. doi:10.1038/s41586-018-0104-4. PMID: 29743672.
BibTeX
@article{peng2018-29743672,
author = {Peng, C. and Gathagan, R. J. and Covell, D. J. and Medellin, C. and Stieber, A. and Robinson, J. L. and Zhang, B. and Pitkin, R. M. and others},
title = {{Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies}},
journal = {Nature},
year = {2018},
doi = {10.1038/s41586-018-0104-4},
pmid = {29743672},
url = {https://doi.org/10.1038/s41586-018-0104-4}
}
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
- GCI-α-Syn and LB-α-Syn show no cell-type preference in seeding α-Syn pathology, which raises the question of why they demonstrate different cell-type distributions in Lewy body disease versus multiple system atrophy.
- We found that oligodendrocytes but not neurons transform misfolded α-Syn into a GCI-like strain, highlighting the fact that distinct α-Syn strains are generated by different intracellular milieus.
Why it matters
Alpha-synuclein clumps taken from multiple system atrophy are more compact than those from Lewy body disease and, in this laboratory work, were about 1,000-fold more potent at seeding new aggregation — a difference the authors call consistent with how aggressive multiple system atrophy is. Neither form preferred one cell type when seeding, yet oligodendrocytes and not neurons converted misfolded alpha-synuclein into the multiple-system-atrophy-like strain, and that strain kept its high seeding activity once in neurons, so the authors conclude strains are set by both the seed and the cell it sits in. This is basic laboratory science: it tests no treatment, measures nothing in patients, and the authors themselves leave open why the diseases differ in which cells are affected.
Study details
- Evidence strengthLow
How this study scored 60/100
Published in a top-tier 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 | 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 | 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 606 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 60.6 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 6 / 6 | Cited 44.1× 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 | 3 / 4 | Cited 174 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Virginia M.‐Y. Lee: h-index 202 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29743672) |
| Free to read | 2 / 2 | Free to read |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
11 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Lewy body dementia
Also tagged “mice”
1,150 studies in the library carry the topic tag “mice”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.