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Cofilin Suppresses Tau-Induced Defects in Dense-Core Granule Formation and Aβ-Induced Neurodegeneration
Verma B, Cording A, Blincowe L, Rice S, Vine H, Wainwright SM, Goberdhan DCI, Wilson C.. bioRxiv, 2026-09-27
Topic: Disease mechanisms in lab and animal studies
Intracellular neurofibrillary tangles formed from hyperphosphorylated tau and extracellular amyloid plaques containing aggregated Aβ-peptides, specific cleavage products of the Amyloid Precursor Protein (APP), are the primary histopathological hallmarks of Alzheimer’s Disease (AD), the leading cause of dementia in humans. However, the initiating steps that lead to these pathologies and early neurodegeneration, and the mechanisms by which tau- and Aβ-induced effects might be linked remain unclear. Using the prostate-like secondary cell (SC) in Drosophila , we recently showed that Aβ modulates normal APP- and membrane-associated protein aggregation in the dense-core granule (DCG) compartments of the regulated secretory pathway by interfering with subsequent membrane:DCG dissociation. This disrupts endolysosomal trafficking and propagates the resulting endolysosomal defects to other cells that endocytose the secreted abnormal DCG proteins. Here we show that overexpressing human tau also disrupts DCG aggregation and membrane:DCG dissociation inside SC secretory compartments, leading to increased endolysosomal targeting of these compartments. In a genetic screen, we find that knockdown of cofilin , which encodes an actin-severing protein required for dynamic remodelling of microfilaments, generates a similar phenotype. Consistent with this, overexpression of Cofilin, which is known to suppress tau-induced neurodegeneration in flies, reduces tau-induced DCG defects in SCs. Indeed, we find that Cofilin overexpression also suppresses Aβ-induced degeneration in the fly eye. We conclude that membrane:DCG aggregate dissociation in DCG compartments is disrupted by both tau- and Aβ-induced genetic changes that are relevant to AD, and this partially involves inhibition of actin cytoskeleton dynamics. Increasing actin remodelling activity can suppress neurodegeneration induced by both tau and Aβ, suggesting that this process provides an important functional link between them that might be targeted therapeutically.
Key findings
- Using the prostate-like secondary cell (SC) in Drosophila , we recently showed that Aβ modulates normal APP- and membrane-associated protein aggregation in the dense-core granule (DCG) compartments of the regulated secretory pathway by interfering with subsequent membrane:DCG dissociation.
- We conclude that membrane:DCG aggregate dissociation in DCG compartments is disrupted by both tau- and Aβ-induced genetic changes that are relevant to AD, and this partially involves inhibition of actin cytoskeleton dynamics.
- Increasing actin remodelling activity can suppress neurodegeneration induced by both tau and Aβ, suggesting that this process provides an important functional link between them that might be targeted therapeutically.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | — / 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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 names 8 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.
APA 7th
Verma, B., Cording, A., Blincowe, L., Rice, S., Vine, H., Wainwright, S. M., et al. (2026). Cofilin Suppresses Tau-Induced Defects in Dense-Core Granule Formation and Aβ-Induced Neurodegeneration. bioRxiv. https://doi.org/10.64898/2026.09.22.753479
Vancouver
Verma B, Cording A, Blincowe L, Rice S, Vine H, Wainwright SM, et al. Cofilin Suppresses Tau-Induced Defects in Dense-Core Granule Formation and Aβ-Induced Neurodegeneration. bioRxiv. 2026. doi:10.64898/2026.09.22.753479.
BibTeX
@article{verma2026-b6245a7d,
author = {Verma, B. and Cording, A. and Blincowe, L. and Rice, S. and Vine, H. and Wainwright, S. M. and Goberdhan, D. C. I. and Wilson, C.},
title = {{Cofilin Suppresses Tau-Induced Defects in Dense-Core Granule Formation and Aβ-Induced Neurodegeneration}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.22.753479},
url = {https://doi.org/10.64898/2026.09.22.753479}
}
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