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Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor
Hemming ML, Selkoe DJ.. The Journal of biological chemistry, 2005-09-09
Topic: Amyloid, tau and blood-test diagnosis
Human genetic data have associated angiotensin-converting enzyme (ACE) with Alzheimer disease (AD), and purified ACE has been reported to cleave synthetic amyloid beta-protein (Abeta) in vitro. Whether deficiency in ACE activity, arising from genetic alteration or pharmacological inhibition, can decrease Abeta degradation and allow Abeta accumulation in intact cells is unknown. We cloned ACE from human neuroblastoma cells and showed that it had posttranslational processing and enzymatic activity typical of the endogenous protease.
Key findings
- Whether deficiency in ACE activity, arising from genetic alteration or pharmacological inhibition, can decrease Abeta degradation and allow Abeta accumulation in intact cells is unknown.
- We cloned ACE from human neuroblastoma cells and showed that it had posttranslational processing and enzymatic activity typical of the endogenous protease.
- Cellular expression of ACE promoted degradation of naturally secreted Abeta40 and Abeta42, leading to significant clearance of both species.
- Using site-directed mutagenesis, we determined that both active sites within ACE contribute to Abeta clearance, and an ACE construct bearing mutations in each catalytic domain had no effect on Abeta levels.
Why it matters
In cells, angiotensin-converting enzyme promoted the breakdown of secreted amyloid beta 40 and 42, and an ACE inhibitor raised amyloid beta levels. This is cell-based evidence that ACE activity affects amyloid clearance, not proof that ACE inhibitors cause or treat Alzheimer's in patients.
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Study details
- Evidence strengthLow
How this study scored 50/100
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 (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 2005 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 333 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.5 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 9.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 44 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Dennis J. Selkoe: h-index 174 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16154999) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.m508460200
- PubMed: 16154999
- Original source →
- Free full text: Journal of Biological Chemistry →
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
Hemming, M. L., & Selkoe, D. J. (2005). Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m508460200
Vancouver
Hemming ML, Selkoe DJ. Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m508460200. PMID: 16154999.
BibTeX
@article{hemming2005-16154999,
author = {Hemming, M. L. and Selkoe, D. J.},
title = {{Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor}},
journal = {The Journal of biological chemistry},
year = {2005},
doi = {10.1074/jbc.m508460200},
pmid = {16154999},
url = {https://doi.org/10.1074/jbc.m508460200}
}
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