Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain
Zhao L, Li Z, Vong JSL, Chen X, Lai HM, Yan LYC, Huang J, Sy SKH et al.. Nature communications, 2020-09-04
Topic: Brain proteins, microglia and lab models
The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovascular dysfunction in neurodegenerative diseases remain elusive. Here, we report zonation-dependent transcriptomic changes in aged mouse brain endothelial cells (ECs), which prominently implicate altered immune/cytokine signaling in ECs of all vascular segments, and functional changes impacting the blood-brain barrier (BBB) and glucose/energy metabolism especially in capillary ECs (capECs). An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains. Treatment with exenatide, a glucagon-like peptide-1 receptor agonist, strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage, with associated attenuation of microglial priming. We thus revealed transcriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible.
Key findings
- The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovascular dysfunction in neurodegenerative diseases remain elusive.
- An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains.
- We thus revealed transcriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible.
Why it matters
In aged mouse brain endothelial cells, age-related gene expression changes involved immune signaling and the blood-brain barrier, and some of these changes overlapped with genes implicated in human Alzheimer's disease. Treatment with exenatide reversed these changes and blood-brain barrier leakage in mice, but this is animal research and does not establish a treatment for people.
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Study details
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (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 | 5 / 7 | Cited 126 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.8 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 5.2× 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 | 3 / 4 | Cited 67 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ho Ko: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Chinese University of Hong Kong: institution h-index 1,100 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32887883) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
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Read the original
- DOI: 10.1038/s41467-020-18249-3
- PubMed: 32887883
- Original source →
- Free full text: Nature Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Zhao, L., Li, Z., Vong, J. S. L., Chen, X., Lai, H. M., Yan, L. Y. C., et al. (2020). Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain. Nature communications. https://doi.org/10.1038/s41467-020-18249-3
Vancouver
Zhao L, Li Z, Vong JSL, Chen X, Lai HM, Yan LYC, et al. Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain. Nature communications. 2020. doi:10.1038/s41467-020-18249-3. PMID: 32887883.
BibTeX
@article{zhao2020-32887883,
author = {Zhao, L. and Li, Z. and Vong, J. S. L. and Chen, X. and Lai, H. M. and Yan, L. Y. C. and Huang, J. and Sy, S. K. H. and others},
title = {{Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain}},
journal = {Nature communications},
year = {2020},
doi = {10.1038/s41467-020-18249-3},
pmid = {32887883},
url = {https://doi.org/10.1038/s41467-020-18249-3}
}
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