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Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation
Buxbaum JD, Gandy SE, Cicchetti P, Ehrlich ME, Czernik AJ, Fracasso RP, Ramabhadran TV, Unterbeck AJ et al.. Proceedings of the National Academy of Sciences of the United States of America, 1990-08-01
Topic: Amyloid, tau and blood-test diagnosis
The turnover and processing of the Alzheimer beta/A4 amyloid precursor protein (beta APP) has been studied in PC12 cells after treatment with agents that regulate protein phosphorylation. Phorbol 12,13-dibutyrate, an agent that stimulates protein kinase C, decreased the levels of mature beta APP and increased the levels of 15- and 19-kDa peptides. These peptides appeared to be COOH-terminal fragments of beta APP, which arose when phorbol 12,13-dibutyrate increased the rate of proteolytic processing of mature forms of beta APP.
Key findings
- Phorbol 12,13-dibutyrate, an agent that stimulates protein kinase C, decreased the levels of mature beta APP and increased the levels of 15- and 19-kDa peptides.
- These peptides appeared to be COOH-terminal fragments of beta APP, which arose when phorbol 12,13-dibutyrate increased the rate of proteolytic processing of mature forms of beta APP.
- Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, also led to decreased levels of mature beta APP and increased levels of the 15- and 19-kDa peptides.
- H-7, an inhibitor of protein kinase C and of several other protein kinases, apparently decreased the rate of proteolytic processing of mature beta APP.
Why it matters
In PC12 cells, a protein kinase C activator (phorbol 12,13-dibutyrate) and a phosphatase inhibitor (okadaic acid) both lowered levels of mature amyloid precursor protein and raised 15- and 19-kDa fragments that "appeared to be COOH-terminal fragments." The kinase inhibitor H-7 "apparently decreased" this processing, which suggests that cell signalling through phosphorylation helps control how the protein is cut. This was a cell-culture experiment with no patients, so it does not show any treatment, cure or prevention for Alzheimer's in people.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 1990 — 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 455 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.0 citations a year over 38 year(s) since 1990 |
| Impact for its field and year | 5 / 6 | Cited 21.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Paul Greengard: h-index 206 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Rockefeller University: institution h-index 1,200 (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 2116015) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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
Buxbaum, J. D., Gandy, S. E., Cicchetti, P., Ehrlich, M. E., Czernik, A. J., Fracasso, R. P., et al. (1990). Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.87.15.6003
Vancouver
Buxbaum JD, Gandy SE, Cicchetti P, Ehrlich ME, Czernik AJ, Fracasso RP, et al. Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proceedings of the National Academy of Sciences of the United States of America. 1990. doi:10.1073/pnas.87.15.6003. PMID: 2116015.
BibTeX
@article{buxbaum1990-2116015,
author = {Buxbaum, J. D. and Gandy, S. E. and Cicchetti, P. and Ehrlich, M. E. and Czernik, A. J. and Fracasso, R. P. and Ramabhadran, T. V. and Unterbeck, A. J. and others},
title = {{Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1990},
doi = {10.1073/pnas.87.15.6003},
pmid = {2116015},
url = {https://doi.org/10.1073/pnas.87.15.6003}
}
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