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Rapidly reversible persistent long-term potentiation inhibition by patient-derived brain tau and amyloid ß proteins
Ondrejcak T, Klyubin I, Hu NW, Yang Y, Zhang Q, Rodriguez BJ, Rowan MJ.. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2024-06-10
Topic: Brain proteins, microglia and lab models
How the two pathognomonic proteins of Alzheimer's disease (AD); amyloid ß (Aß) and tau, cause synaptic failure remains enigmatic. Certain synthetic and recombinant forms of these proteins are known to act concurrently to acutely inhibit long-term potentiation (LTP). Here, we examined the effect of early amyloidosis on the acute disruptive action of synaptotoxic tau prepared from recombinant protein and tau in patient-derived aqueous brain extracts. We also explored the persistence of the inhibition of LTP by different synaptotoxic tau preparations. A single intracerebral injection of aggregates of recombinant human tau that had been prepared by either sonication of fibrils (SτAs) or disulfide bond formation (oTau) rapidly and persistently inhibited LTP in rat hippocampus. The threshold for the acute inhibitory effect of oTau was lowered in amyloid precursor protein (APP)-transgenic rats. A single injection of synaptotoxic tau-containing AD or Pick's disease brain extracts also inhibited LTP, for over two weeks. Remarkably, the persistent disruption of synaptic plasticity by patient-derived brain tau was rapidly reversed by a single intracerebral injection of different anti-tau monoclonal antibodies, including one directed to a specific human tau amino acid sequence. We conclude that patient-derived LTP-disrupting tau species persist in the brain for weeks, maintaining their neuroactivity often in concert with Aß. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
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APA 7th
Ondrejcak, T., Klyubin, I., Hu, N. W., Yang, Y., Zhang, Q., Rodriguez, B. J., et al. (2024). Rapidly reversible persistent long-term potentiation inhibition by patient-derived brain tau and amyloid ß proteins. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. https://doi.org/10.1098/rstb.2023.0234
Vancouver
Ondrejcak T, Klyubin I, Hu NW, Yang Y, Zhang Q, Rodriguez BJ, et al. Rapidly reversible persistent long-term potentiation inhibition by patient-derived brain tau and amyloid ß proteins. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2024. doi:10.1098/rstb.2023.0234. PMID: 38853565.
BibTeX
@article{ondrejcak2024-38853565,
author = {Ondrejcak, T. and Klyubin, I. and Hu, N. W. and Yang, Y. and Zhang, Q. and Rodriguez, B. J. and Rowan, M. J.},
title = {{Rapidly reversible persistent long-term potentiation inhibition by patient-derived brain tau and amyloid ß proteins}},
journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences},
year = {2024},
doi = {10.1098/rstb.2023.0234},
pmid = {38853565},
url = {https://doi.org/10.1098/rstb.2023.0234}
}
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 7 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.
Key findings
- We conclude that patient-derived LTP-disrupting tau species persist in the brain for weeks, maintaining their neuroactivity often in concert with Aß.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Philosophical transactions of the Royal Society of London. Series B, Biological sciences) |
| 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 | 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 | — / 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 38853565) |
| 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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