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Rab11-exosome biogenesis regulators mediate Aβ-induced intercellular propagation of endolysosomal trafficking defects and neurodegeneration
Cording A, Verma B, Arous A, Rice S, Vine H, Blincowe L, Wainwright SM, Singh PJ et al.. bioRxiv, 2026-09-20
Topic: Disease mechanisms in lab and animal studies
Alzheimer’s Disease (AD) is characterised by two histopathological hallmarks, intracellular tau-containing neurofibrillary tangles and extracellular amyloid plaques containing β-amyloid (Aβ), a specific cleavage product of Amyloid Precursor Protein (APP). Initiation of Aβ-induced neuronal pathology, however, has been postulated to involve intracellular events affecting endolysosomal trafficking that can propagate between cells. Recent studies in non-neuronal Drosophila secondary cells (SCs) have revealed that Aβ interferes with APP-regulated protein aggregation events, which package signalling molecules into insoluble dense-core granules (DCGs) during normal regulated secretion, inducing endolysosomal defects that are transferred to other cells. Here, using SCs, we show that knockdown of the gene encoding accessory ESCRT-III protein Chmp5, which selectively regulates the formation of intraluminal vesicles (ILVs) inside SC DCG compartments that are subsequently released as Rab11-exosomes, inhibits propagation of Aβ-induced endolysosomal trafficking defects. Furthermore, knocking down Chmp5 or other accessory ESCRT-III genes also suppresses Aβ-induced, neurodegeneration-dependent morphological defects in the Drosophila eye. We conclude that genes controlling the Rab11-exosome biogenesis pathway play a key role in both Aβ-induced endolysosomal trafficking defects associated with aberrant regulated secretion and cellular events leading to neurodegeneration. Our findings indicate these processes are linked and may suggest new target pathways for future development of AD therapeutics.
Key findings
- Recent studies in non-neuronal Drosophila secondary cells (SCs) have revealed that Aβ interferes with APP-regulated protein aggregation events, which package signalling molecules into insoluble dense-core granules (DCGs) during normal regulated secretion, inducing endolysosomal defects that are transferred to other cells.
- We conclude that genes controlling the Rab11-exosome biogenesis pathway play a key role in both Aβ-induced endolysosomal trafficking defects associated with aberrant regulated secretion and cellular events leading to neurodegeneration.
- Our findings indicate these processes are linked and may suggest new target pathways for future development of AD therapeutics.
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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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APA 7th
Cording, A., Verma, B., Arous, A., Rice, S., Vine, H., Blincowe, L., et al. (2026). Rab11-exosome biogenesis regulators mediate Aβ-induced intercellular propagation of endolysosomal trafficking defects and neurodegeneration. bioRxiv. https://doi.org/10.64898/2026.09.17.752336
Vancouver
Cording A, Verma B, Arous A, Rice S, Vine H, Blincowe L, et al. Rab11-exosome biogenesis regulators mediate Aβ-induced intercellular propagation of endolysosomal trafficking defects and neurodegeneration. bioRxiv. 2026. doi:10.64898/2026.09.17.752336.
BibTeX
@article{cording2026-f93c5f98,
author = {Cording, A. and Verma, B. and Arous, A. and Rice, S. and Vine, H. and Blincowe, L. and Wainwright, S. M. and Singh, P. J. and others},
title = {{Rab11-exosome biogenesis regulators mediate Aβ-induced intercellular propagation of endolysosomal trafficking defects and neurodegeneration}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.17.752336},
url = {https://doi.org/10.64898/2026.09.17.752336}
}