Home › Research › Vascular contributions
Neurodegeneration-inducing macromolecules exit the brain via nanovascular conduits formed by reticular fibroblasts
Nortley R, Anderle S, Sideris-Lampretsas G, Davis H, Sethi H, Alasaadi DN, Acton S, Attwell D.. bioRxiv, 2026-09-27
Topic: Inflammation, microglia and astrocytes
Accumulation of proteins such as amyloid β (Aβ), hyperphosphorylated tau and α-synuclein within the brain alters neural information processing and causes neurodegeneration 1–3 , but how toxic solutes are cleared from the brain remains highly controversial 4,5 . Proposed exit routes include efflux across endothelial cells into the blood 6,7 , and movement to the pial surface via vasomotion-induced pumping along spaces within arteriolar smooth muscle 8 or via outflow along the perivascular space of ascending venules promoted by water flux through astrocytes (the glymphatic system 9 ). From the pial surface of the brain, drainage may continue to dural lymphatics, along the outer sheaths of exiting cranial nerves and across the cribriform plate 10–14 . We now report the presence, in mice and humans, of 2 μm diameter conduits that remove fluorescently labelled tau and Aβ from the brain. These conduits form a spatially-organised mesh within the walls of penetrating arterioles and pial arteries, and around the surface of ascending venules and deep cerebral and pial veins. They course through the pial and arachnoid layers to span the CSF space, wrapping the brain and cranial nerves. They are formed of reticular fibroblasts, which label for VE-cadherin 15 and PDGFRα 16 , the lymphatic markers 17 podoplanin, VEGFR3 and Prox1, and reticular fibroblast extracellular matrix components collagen I and VI 16,18–20 . Parenchymal tau drains from the brain at a similar rate via arteriolar conduits and via conduits around venules, arguing against preferential removal by a glymphatic mechanism. In Alzheimer’s disease model mice, Aβ is seen traversing these lymph node-like conduits. Modulation of molecular transfer via this route may accelerate or delay cognitive decline, and slowed transfer from arteriolar to pial-arachnoid conduits may initiate cerebral amyloid angiopathy.
Key findings
- They course through the pial and arachnoid layers to span the CSF space, wrapping the brain and cranial nerves.
- They are formed of reticular fibroblasts, which label for VE-cadherin 15 and PDGFRα 16 , the lymphatic markers 17 podoplanin, VEGFR3 and Prox1, and reticular fibroblast extracellular matrix components collagen I and VI 16,18–20 .
- Parenchymal tau drains from the brain at a similar rate via arteriolar conduits and via conduits around venules, arguing against preferential removal by a glymphatic mechanism.
- In Alzheimer’s disease model mice, Aβ is seen traversing these lymph node-like conduits.
- Modulation of molecular transfer via this route may accelerate or delay cognitive decline, and slowed transfer from arteriolar to pial-arachnoid conduits may initiate cerebral amyloid angiopathy.
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. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Nortley, R., Anderle, S., Sideris-Lampretsas, G., Davis, H., Sethi, H., Alasaadi, D. N., et al. (2026). Neurodegeneration-inducing macromolecules exit the brain via nanovascular conduits formed by reticular fibroblasts. bioRxiv. https://doi.org/10.64898/2026.09.21.752863
Vancouver
Nortley R, Anderle S, Sideris-Lampretsas G, Davis H, Sethi H, Alasaadi DN, et al. Neurodegeneration-inducing macromolecules exit the brain via nanovascular conduits formed by reticular fibroblasts. bioRxiv. 2026. doi:10.64898/2026.09.21.752863.
BibTeX
@article{nortley2026-211812a0,
author = {Nortley, R. and Anderle, S. and Sideris-Lampretsas, G. and Davis, H. and Sethi, H. and Alasaadi, D. N. and Acton, S. and Attwell, D.},
title = {{Neurodegeneration-inducing macromolecules exit the brain via nanovascular conduits formed by reticular fibroblasts}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.21.752863},
url = {https://doi.org/10.64898/2026.09.21.752863}
}