ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components
Yamazaki Y, Shinohara M, Yamazaki A, Ren Y, Asmann YW, Kanekiyo T, Bu G.. Arteriosclerosis, thrombosis, and vascular biology, 2019-10-31
Topic: Brain proteins, microglia and lab models
Objective The ε4 allele of the APOE gene ( APOE4 ) is the strongest genetic risk factor for Alzheimer disease when compared with the common ε3 allele. Although there has been significant progress in understanding how apoE4 (apolipoprotein E4) drives amyloid pathology, its effects on amyloid-independent pathways, in particular cerebrovascular integrity and function, are less clear. Approach and Results: Here, we show that brain pericytes, the mural cells of the capillary walls, differentially modulate endothelial cell phenotype in an apoE isoform-dependent manner. Extracellular matrix protein induction, tube-like structure formation, and barrier formation were lower with endothelial cells cocultured with pericytes isolated from apoE4-targeted replacement (TR) mice compared with those from apoE3-TR mice. Importantly, aged apoE4-targeted replacement mice had decreased extracellular matrix protein expression and increased plasma protein leakages compared with apoE3-TR mice. Conclusions ApoE4 impairs pericyte-mediated basement membrane formation, potentially contributing to the cerebrovascular effects of apoE4.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Yamazaki, Y., Shinohara, M., Yamazaki, A., Ren, Y., Asmann, Y. W., Kanekiyo, T., et al. (2020). ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components. Arteriosclerosis, thrombosis, and vascular biology. https://doi.org/10.1161/atvbaha.119.313169
Vancouver
Yamazaki Y, Shinohara M, Yamazaki A, Ren Y, Asmann YW, Kanekiyo T, et al. ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components. Arteriosclerosis, thrombosis, and vascular biology. 2020. doi:10.1161/atvbaha.119.313169. PMID: 31665905.
BibTeX
@article{yamazaki2020-31665905,
author = {Yamazaki, Y. and Shinohara, M. and Yamazaki, A. and Ren, Y. and Asmann, Y. W. and Kanekiyo, T. and Bu, G.},
title = {{ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components}},
journal = {Arteriosclerosis, thrombosis, and vascular biology},
year = {2020},
doi = {10.1161/atvbaha.119.313169},
pmid = {31665905},
url = {https://doi.org/10.1161/atvbaha.119.313169}
}
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 7 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
- Objective The ε4 allele of the APOE gene ( APOE4 ) is the strongest genetic risk factor for Alzheimer disease when compared with the common ε3 allele.
- Although there has been significant progress in understanding how apoE4 (apolipoprotein E4) drives amyloid pathology, its effects on amyloid-independent pathways, in particular cerebrovascular integrity and function, are less clear.
- Approach and Results: Here, we show that brain pericytes, the mural cells of the capillary walls, differentially modulate endothelial cell phenotype in an apoE isoform-dependent manner.
- Extracellular matrix protein induction, tube-like structure formation, and barrier formation were lower with endothelial cells cocultured with pericytes isolated from apoE4-targeted replacement (TR) mice compared with those from apoE3-TR mice.
- Importantly, aged apoE4-targeted replacement mice had decreased extracellular matrix protein expression and increased plasma protein leakages compared with apoE3-TR mice.
Why it matters
In mice with different human APOE versions, apoE4 in brain pericytes impaired basement membrane formation and increased plasma protein leakage compared with apoE3. This is animal research on a possible amyloid-independent effect of apoE4 and does not show any treatment for people.
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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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Arteriosclerosis, thrombosis, and vascular biology) |
| Journal's citation record | 3 / 4 | Arteriosclerosis Thrombosis and Vascular Biology: journal h-index 340 (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 | 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 | 2 / 5 | 2020 — within 10 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 | 4 / 7 | Cited 88 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.0 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 2 / 6 | Cited 2.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 39 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Guojun Bu: h-index 120 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31665905) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 45 / 100 | — |
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