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Characterization of the Tau Interactome in Human Brain Reveals Isoform-Dependent Interaction with 14-3-3 Family Proteins
Betters RK, Luhmann E, Gottschalk AC, Xu Z, Ptak CP, Fiock KL, Radoshevich LC, Hefti MM.. eNeuro, 2022-10-18
Topic: Brain proteins, microglia and lab models
Tau phosphorylation and aggregation is the final common pathway for neuronal toxicity across multiple neurodegenerative diseases including Alzheimer disease, progressive supranuclear palsy, and corticobasal degeneration. We have previously shown that the fetal brain expresses high levels of phosphorylated tau, and even tau aggregates, without apparent toxic effects. The mechanisms for this remarkable resilience, however, remain unclear.
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APA 7th
Betters, R. K., Luhmann, E., Gottschalk, A. C., Xu, Z., Ptak, C. P., Fiock, K. L., et al. (2022). Characterization of the Tau Interactome in Human Brain Reveals Isoform-Dependent Interaction with 14-3-3 Family Proteins. eNeuro. https://doi.org/10.1101/2022.10.17.512532
Vancouver
Betters RK, Luhmann E, Gottschalk AC, Xu Z, Ptak CP, Fiock KL, et al. Characterization of the Tau Interactome in Human Brain Reveals Isoform-Dependent Interaction with 14-3-3 Family Proteins. eNeuro. 2022. doi:10.1101/2022.10.17.512532.
BibTeX
@article{betters2022-5909f2fc,
author = {Betters, R. K. and Luhmann, E. and Gottschalk, A. C. and Xu, Z. and Ptak, C. P. and Fiock, K. L. and Radoshevich, L. C. and Hefti, M. M.},
title = {{Characterization of the Tau Interactome in Human Brain Reveals Isoform-Dependent Interaction with 14-3-3 Family Proteins}},
journal = {eNeuro},
year = {2022},
doi = {10.1101/2022.10.17.512532},
url = {https://doi.org/10.1101/2022.10.17.512532}
}
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Key findings
- We have previously shown that the fetal brain expresses high levels of phosphorylated tau, and even tau aggregates, without apparent toxic effects.
- The mechanisms for this remarkable resilience, however, remain unclear.
- In order to identify potential mediators of this resilience, we used bead-linked total tau immunoprecipitation in human fetal, adult, and Alzheimer disease brains.
- We then used heterologous transfection in HEK 293T cells followed by coimmunoprecipitation, mass photometry, and nuclear magnetic resonance (NMR) to further characterize the interaction of tau with one of our top hits, 14-3-3-β.
Why it matters
This study characterized the tau interactome in human fetal, adult and Alzheimer's disease brains and found isoform-dependent interaction with 14-3-3 family proteins, aiming to explain why fetal phosphorylated tau and aggregates appear non-toxic. It is laboratory work on mechanisms and does not test any treatment, cure or prevention.
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Study details
- Evidence strengthLow
How this study scored 36/100
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, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 23 of the 64 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (eNeuro) |
| 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 | 3 / 5 | 2022 — within 6 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 | 0 / 6 | No other study in this library cites it |
| 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 36898832) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 64 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 23 of the 64 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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Also tagged “phosphorylated”
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