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Dextran sulphate-induced tau assemblies cause endogenous tau aggregation and propagation in wild-type mice
Masuda-Suzukake M, Suzuki G, Hosokawa M, Nonaka T, Goedert M, Hasegawa M.. Brain communications, 2020-07-08
Topic: Brain proteins, microglia and lab models
Accumulation of assembled tau protein in the central nervous system is characteristic of Alzheimer's disease and several other neurodegenerative diseases, called tauopathies. Recent studies have revealed that propagation of assembled tau is key to understanding the pathological mechanisms of these diseases. Mouse models of tau propagation are established by injecting human-derived tau seeds intracerebrally; nevertheless, these have a limitation in terms of regulation of availability. To date, no study has shown that synthetic assembled tau induce tau propagation in non-transgenic mice. Here we confirm that dextran sulphate, a sulphated glycosaminoglycan, induces the assembly of recombinant tau protein into filaments in vitro . As compared to tau filaments induced by heparin, those induced by dextran sulphate showed higher thioflavin T fluorescence and lower resistance to guanidine hydrochloride, which suggests that the two types of filaments have distinct conformational features. Unlike other synthetic filament seeds, intracerebral injection of dextran sulphate-induced assemblies of recombinant tau caused aggregation of endogenous murine tau in wild-type mice. AT8-positive tau was present at the injection site 1 month after injection, from where it spread to anatomically connected regions. Induced tau assemblies were also stained by anti-tau antibodies AT100, AT180, 12E8, PHF1, anti-pS396 and anti-pS422. They were thioflavin- and Gallyas-Braak silver-positive, indicative of amyloid. In biochemical analyses, accumulated sarkosyl-insoluble and hyperphosphorylated tau was observed in the injected mice. In conclusion, we revealed that intracerebral injection of synthetic full-length wild-type tau seeds prepared in the presence of dextran sulphate caused tau propagation in non-transgenic mice. These findings establish that propagation of tau assemblies does not require tau to be either mutant and/or overexpressed.
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APA 7th
Masuda-Suzukake, M., Suzuki, G., Hosokawa, M., Nonaka, T., Goedert, M., & Hasegawa, M. (2020). Dextran sulphate-induced tau assemblies cause endogenous tau aggregation and propagation in wild-type mice. Brain communications. https://doi.org/10.1093/braincomms/fcaa091
Vancouver
Masuda-Suzukake M, Suzuki G, Hosokawa M, Nonaka T, Goedert M, Hasegawa M. Dextran sulphate-induced tau assemblies cause endogenous tau aggregation and propagation in wild-type mice. Brain communications. 2020. doi:10.1093/braincomms/fcaa091. PMID: 33005889.
BibTeX
@article{masudasuzukake2020-33005889,
author = {Masuda-Suzukake, M. and Suzuki, G. and Hosokawa, M. and Nonaka, T. and Goedert, M. and Hasegawa, M.},
title = {{Dextran sulphate-induced tau assemblies cause endogenous tau aggregation and propagation in wild-type mice}},
journal = {Brain communications},
year = {2020},
doi = {10.1093/braincomms/fcaa091},
pmid = {33005889},
url = {https://doi.org/10.1093/braincomms/fcaa091}
}
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Key findings
- Recent studies have revealed that propagation of assembled tau is key to understanding the pathological mechanisms of these diseases.
- To date, no study has shown that synthetic assembled tau induce tau propagation in non-transgenic mice.
- As compared to tau filaments induced by heparin, those induced by dextran sulphate showed higher thioflavin T fluorescence and lower resistance to guanidine hydrochloride, which suggests that the two types of filaments have distinct conformational features.
- In conclusion, we revealed that intracerebral injection of synthetic full-length wild-type tau seeds prepared in the presence of dextran sulphate caused tau propagation in non-transgenic mice.
- These findings establish that propagation of tau assemblies does not require tau to be either mutant and/or overexpressed.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 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 “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33005889) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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