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Endothelial nitric oxide modulates expression and processing of amyloid precursor protein
Austin SA, Santhanam AV, Katusic ZS.. Circulation research, 2010-12-02
Topic: Brain proteins, microglia and lab models
Rationale the exact etiology of sporadic Alzheimer disease (AD) is unclear, but it is interesting that several cardiovascular risk factors are associated with higher incidence of AD. The link between these risk factors and AD has yet to be identified; however, a common feature is endothelial dysfunction, specifically, decreased bioavailability of nitric oxide (NO). Objective to determine the relationship between endothelial derived NO and the expression and processing of amyloid precursor protein (APP).
Key findings
- The link between these risk factors and AD has yet to be identified; however, a common feature is endothelial dysfunction, specifically, decreased bioavailability of nitric oxide (NO).
- Objective to determine the relationship between endothelial derived NO and the expression and processing of amyloid precursor protein (APP).
- Methods and results we used human brain microvascular endothelial cells to examine the role of NO in modulating APP expression and processing in vitro.
- Inhibition of endothelial nitric oxide synthase (eNOS) with the specific NOS inhibitor L-NAME (N(G)-nitro-l-arginine methyl ester) led to increased APP and BACE1 (β-site APP-cleaving enzyme1) protein levels, as well as increased secretion of the amyloidogenic peptide amyloid β (Aβ) (control 10.93 ± 0.70 pg/mL; L-NAME 168.21 ± 27.38 pg/mL; P<0.001).
Why it matters
In human brain blood-vessel cells grown in the lab, blocking the enzyme that makes nitric oxide raised levels of APP and of BACE1, the enzyme that starts cutting APP into amyloid beta, and increased secreted amyloid beta from 10.93 to 168.21 pg/mL. The authors set out to probe why cardiovascular risk factors, which share reduced nitric oxide in blood vessels, are associated with more Alzheimer's. This is a single cell-culture experiment, not evidence from people and not a treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 46/100
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 (Circulation research) |
| Journal's citation record | 4 / 4 | Circulation Research: journal h-index 507 (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 | 1 / 5 | 2010 — within 20 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 187 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.4 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 4 / 6 | Cited 8.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Zvonimir S. Katušić: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21127294) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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Read the original
- DOI: 10.1161/circresaha.110.233080
- PubMed: 21127294
- Original source →
- Free full text: Circulation Research →
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. Check the citation against the original before you use it.
APA 7th
Austin, S. A., Santhanam, A. V., & Katusic, Z. S. (2010). Endothelial nitric oxide modulates expression and processing of amyloid precursor protein. Circulation research. https://doi.org/10.1161/circresaha.110.233080
Vancouver
Austin SA, Santhanam AV, Katusic ZS. Endothelial nitric oxide modulates expression and processing of amyloid precursor protein. Circulation research. 2010. doi:10.1161/circresaha.110.233080. PMID: 21127294.
BibTeX
@article{austin2010-21127294,
author = {Austin, S. A. and Santhanam, A. V. and Katusic, Z. S.},
title = {{Endothelial nitric oxide modulates expression and processing of amyloid precursor protein}},
journal = {Circulation research},
year = {2010},
doi = {10.1161/circresaha.110.233080},
pmid = {21127294},
url = {https://doi.org/10.1161/circresaha.110.233080}
}
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