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A pericyte-to-myofibroblast transition links APOE4 to cerebrovascular degeneration
Braxton R Schuldt, Dominic Haworth-Staines, Andrea Perez-Arevalo, Diede W M Broekaart, Ashley Harlock, Leon Wang, Anna Bright, Georgia Gallagher et al.. Cell, 2026-09-24
Topic: Inflammation, microglia and astrocytes
Cerebrovascular disease is a major but poorly understood feature of Alzheimer's disease (AD). The strongest genetic AD risk factor, apolipoprotein E4 (APOE4), is associated with cerebrovascular degeneration, including vascular amyloid deposition and fibrosis. To uncover how APOE4 promotes cerebrovascular pathology, we assembled a single-cell transcriptomic atlas of human brain vasculature. In APOE4 carriers, pericyte abundance was significantly reduced and accompanied by the emergence of a myofibroblast-like cell population co-expressing contraction and extracellular matrix genes. Immunostaining confirmed non-vascular myofibroblasts in APOE4 human and mouse brains. We show that APOE4 pericytes transition into myofibroblasts that secrete fibronectin, which promotes vascular amyloid accumulation. Computational and experimental analyses identified elevated transforming growth factor β (TGF-β) signaling as the driver of this pericyte-to-myofibroblast transition. Inhibition of TGF-β restored pericyte coverage and reduced vascular fibrosis and amyloid to APOE3 levels, revealing a targetable mechanism linking APOE4 to cerebrovascular pathology in AD.
Key findings
- The strongest genetic AD risk factor, apolipoprotein E4 (APOE4), is associated with cerebrovascular degeneration, including vascular amyloid deposition and fibrosis.
- In APOE4 carriers, pericyte abundance was significantly reduced and accompanied by the emergence of a myofibroblast-like cell population co-expressing contraction and extracellular matrix genes.
Study details
- Evidence strengthLow
How this study scored 45/100
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 journal's citation record, 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, multi-centre collaboration and free to read, so those were left out: it earned 25 of the 56 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 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 | 2 / 2 | Indexed in PubMed (PMID 42785300) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 25 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 25 of the 56 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Schuldt, B. R., Haworth-Staines, D., Perez-Arevalo, A., Broekaart, D. W. M., Harlock, A., Wang, L., et al. (2026). A pericyte-to-myofibroblast transition links APOE4 to cerebrovascular degeneration. Cell. https://doi.org/10.1016/j.cell.2026.08.058
Vancouver
Schuldt BR, Haworth-Staines D, Perez-Arevalo A, Broekaart DWM, Harlock A, Wang L, et al. A pericyte-to-myofibroblast transition links APOE4 to cerebrovascular degeneration. Cell. 2026. doi:10.1016/j.cell.2026.08.058. PMID: 42785300.
BibTeX
@article{schuldt2026-42785300,
author = {Schuldt, Braxton R and Haworth-Staines, Dominic and Perez-Arevalo, Andrea and Broekaart, Diede W M and Harlock, Ashley and Wang, Leon and Bright, Anna and Gallagher, Georgia and others},
title = {{A pericyte-to-myofibroblast transition links APOE4 to cerebrovascular degeneration}},
journal = {Cell},
year = {2026},
doi = {10.1016/j.cell.2026.08.058},
pmid = {42785300},
url = {https://doi.org/10.1016/j.cell.2026.08.058}
}
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