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Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration
Tracy TE, Madero-Pérez J, Swaney DL, Chang TS, Moritz M, Konrad C, Ward ME, Stevenson E et al.. Cell, 2022-01-20
Topic: Brain proteins, microglia and lab models
Tau (MAPT) drives neuronal dysfunction in Alzheimer disease (AD) and other tauopathies. To dissect the underlying mechanisms, we combined an engineered ascorbic acid peroxidase (APEX) approach with quantitative affinity purification mass spectrometry (AP-MS) followed by proximity ligation assay (PLA) to characterize Tau interactomes modified by neuronal activity and mutations that cause frontotemporal dementia (FTD) in human induced pluripotent stem cell (iPSC)-derived neurons. We established interactions of Tau with presynaptic vesicle proteins during activity-dependent Tau secretion and mapped the Tau-binding sites to the cytosolic domains of integral synaptic vesicle proteins. We showed that FTD mutations impair bioenergetics and markedly diminished Tau's interaction with mitochondria proteins, which were downregulated in AD brains of multiple cohorts and correlated with disease severity. These multimodal and dynamic Tau interactomes with exquisite spatial resolution shed light on Tau's role in neuronal function and disease and highlight potential therapeutic targets to block Tau-mediated pathogenesis.
Key findings
- We showed that FTD mutations impair bioenergetics and markedly diminished Tau's interaction with mitochondria proteins, which were downregulated in AD brains of multiple cohorts and correlated with disease severity.
Why it matters
This study mapped how tau interacts with synaptic and mitochondrial proteins in human stem-cell-derived neurons, and found that FTD mutations impaired bioenergetics and reduced tau's interaction with mitochondrial proteins. It is a laboratory study and does not test any treatment or prevention for Alzheimer's disease, so it has no direct implications for treating, curing, or preventing the disease.
Study details
- Evidence strengthLow
How this study scored 58/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| Journal's citation record | 4 / 4 | Cell: journal h-index 1,220 (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 | 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 | 6 / 7 | Cited 348 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 58.0 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 5 / 6 | Cited 35.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 4 / 4 | Cited 239 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Li Gan: h-index 71 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35063084) |
| Free to read | 2 / 2 | Free to read |
| Total | 58 / 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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Tracy, T. E., Madero-Pérez, J., Swaney, D. L., Chang, T. S., Moritz, M., Konrad, C., et al. (2022). Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell. https://doi.org/10.1016/j.cell.2021.12.041
Vancouver
Tracy TE, Madero-Pérez J, Swaney DL, Chang TS, Moritz M, Konrad C, et al. Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell. 2022. doi:10.1016/j.cell.2021.12.041. PMID: 35063084.
BibTeX
@article{tracy2022-35063084,
author = {Tracy, T. E. and Madero-Pérez, J. and Swaney, D. L. and Chang, T. S. and Moritz, M. and Konrad, C. and Ward, M. E. and Stevenson, E. and others},
title = {{Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration}},
journal = {Cell},
year = {2022},
doi = {10.1016/j.cell.2021.12.041},
pmid = {35063084},
url = {https://doi.org/10.1016/j.cell.2021.12.041}
}
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