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Arc mediates intercellular tau transmission via extracellular vesicles
Tyagi M, de Hoog E, Grega M, Sullivan KR, Walker AC, Chadha R, Northrop A, Fábián B, Hummer G, Fuxreiter M, Hyman BT, Shepherd JD. Cell, 2026-06-29
Topic: Brain proteins, microglia and lab models
Tau pathology spreads cell to cell, but the mechanisms of intercellular tau transmission remain unclear. We find that the neuronal gene Arc is critical for the release of tau in neuronal extracellular vesicles (EVs) via a direct protein-protein interaction. Brain EVs purified from transgenic rTg4510 mutant tau mice (rTg WT ) crossed with Arc knockout mice (rTg Arc KO ) contain less tau and reduced tau seeding potential. Both Arc and tau are co-packaged in mouse and human brain-derived EVs. Moreover, Arc levels in brain-derived EVs isolated from human Alzheimer's disease (AD) brains show a strong positive correlation with phosphorylated EV-tau levels. rTg Arc KO mice have increased accumulation of intracellular tau and a modest increase in cell toxicity early in disease progression. Strikingly, intercellular tau transmission is almost absent in Arc KO mice. These results show that Arc is critical for the packaging of tau in EVs, which plays a significant role in intercellular tau transmission.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tyagi, M., de Hoog, E., Grega, M., Sullivan, K. R., Walker, A. C., Chadha, R., et al. (2026). Arc mediates intercellular tau transmission via extracellular vesicles. Cell. https://doi.org/10.1016/j.cell.2026.06.008
Vancouver
Tyagi M, de Hoog E, Grega M, Sullivan KR, Walker AC, Chadha R, et al. Arc mediates intercellular tau transmission via extracellular vesicles. Cell. 2026. doi:10.1016/j.cell.2026.06.008. PMID: 42372723.
BibTeX
@article{tyagi2026-42372723,
author = {Tyagi, M. and de Hoog, E. and Grega, M. and Sullivan, K. R. and Walker, A. C. and Chadha, R. and Northrop, A. and Fábián, B. and Hummer, G. and Fuxreiter, M. and Hyman, B. T. and Shepherd, J. D.},
title = {{Arc mediates intercellular tau transmission via extracellular vesicles}},
journal = {Cell},
year = {2026},
doi = {10.1016/j.cell.2026.06.008},
pmid = {42372723},
url = {https://doi.org/10.1016/j.cell.2026.06.008}
}
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 12 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
- These results show that Arc is critical for the packaging of tau in EVs, which plays a significant role in intercellular tau transmission.
Why it matters
This work found that the neuronal gene Arc is critical for packaging tau into extracellular vesicles and for intercellular tau transmission, with intercellular tau transmission almost absent in Arc knockout mice. These are animal and cell findings about how tau spreads, not a treatment, cure or prevention for Alzheimer's disease.
Study details
- Evidence strengthEarly
Limitations
Phenotypes in Arc knockout mice could arise from indirect effects of Arc loss, such as altered neuronal activity; causal mechanistic studies were limited to transgenic mice expressing mutant human tau at high levels, although Arc and tau were observed together in human brain-derived vesicles.
How this study scored 49/100
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 free to read, so that was left out: it earned 48 of the 98 points we could judge it on, which is 49 out of 100.
| 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 | 2 / 5 | Rated “early” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 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 | 2 / 7 | Cited 13 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 6 / 6 | Cited 41.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jason D. Shepherd: h-index 28 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42372723) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 48 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 48 of the 98 points we could judge it on is 49 out of 100. |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
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