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Prion-like spreading of pathological α-synuclein in brain
Masuda-Suzukake M, Nonaka T, Hosokawa M, Oikawa T, Arai T, Akiyama H, Mann DM, Hasegawa M.. Brain : a journal of neurology, 2013-03-06
Topic: Brain proteins, microglia and lab models
α-Synuclein is the major component of filamentous inclusions that constitute the defining characteristic of neurodegenerative α-synucleinopathies. However, the molecular mechanisms underlying α-synuclein accumulation and spread are unclear. Here we show that intracerebral injections of sarkosyl-insoluble α-synuclein from brains of patients with dementia with Lewy bodies induced hyperphosphorylated α-synuclein pathology in wild-type mice. Furthermore, injection of fibrils of recombinant human and mouse α-synuclein efficiently induced similar α-synuclein pathologies in wild-type mice. C57BL/6J mice injected with α-synuclein fibrils developed abundant Lewy body/Lewy neurite-like pathology, whereas mice injected with soluble α-synuclein did not. Immunoblot analysis demonstrated that endogenous mouse α-synuclein started to accumulate 3 months after inoculation, while injected human α-synuclein fibrils disappeared in about a week. These results indicate that α-synuclein fibrils have prion-like properties and inoculation into wild-type brain induces α-synuclein pathology in vivo. This is a new mouse model of sporadic α-synucleinopathy and should be useful for elucidating progression mechanisms and evaluating disease-modifying therapy.
Key findings
- Immunoblot analysis demonstrated that endogenous mouse α-synuclein started to accumulate 3 months after inoculation, while injected human α-synuclein fibrils disappeared in about a week.
- These results indicate that α-synuclein fibrils have prion-like properties and inoculation into wild-type brain induces α-synuclein pathology in vivo.
Why it matters
In normal mice, injecting clumped (fibril) alpha-synuclein — taken from the brains of people with dementia with Lewy bodies, or made in the lab — set off Lewy-body-like changes, while injecting the non-clumped (soluble) form did not. The injected human protein was gone in about a week, yet the mice's own alpha-synuclein began building up about 3 months later, which the authors read as evidence the clumps act in a "prion-like" way. It gives researchers a mouse model for studying how this disease progresses and for testing future treatments; it is animal research, tested no treatment, and does not show the disease passes between people.
Study details
- Evidence strengthLow
How this study scored 56/100
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 (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 2013 — within 20 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 869 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 57.9 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 5 / 6 | Cited 37.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 3 / 4 | Cited 154 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Masato Hasegawa: h-index 97 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Manchester: institution h-index 1,304 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23466394) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 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).
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Masuda-Suzukake, M., Nonaka, T., Hosokawa, M., Oikawa, T., Arai, T., Akiyama, H., et al. (2013). Prion-like spreading of pathological α-synuclein in brain. Brain : a journal of neurology. https://doi.org/10.1093/brain/awt037
Vancouver
Masuda-Suzukake M, Nonaka T, Hosokawa M, Oikawa T, Arai T, Akiyama H, et al. Prion-like spreading of pathological α-synuclein in brain. Brain : a journal of neurology. 2013. doi:10.1093/brain/awt037. PMID: 23466394.
BibTeX
@article{masudasuzukake2013-23466394,
author = {Masuda-Suzukake, M. and Nonaka, T. and Hosokawa, M. and Oikawa, T. and Arai, T. and Akiyama, H. and Mann, D. M. and Hasegawa, M.},
title = {{Prion-like spreading of pathological α-synuclein in brain}},
journal = {Brain : a journal of neurology},
year = {2013},
doi = {10.1093/brain/awt037},
pmid = {23466394},
url = {https://doi.org/10.1093/brain/awt037}
}
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