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Beta-amyloid precursor protein cleavage by a membrane-bound protease
Sisodia SS.. Proceedings of the National Academy of Sciences of the United States of America, 1992-07-01
Topic: Brain proteins, microglia and lab models
The principal component of amyloid plaques in Alzheimer disease is beta-amyloid protein, an approximately 4-kDa peptide derived from amyloid precursor proteins. Previous studies have established that amyloid precursor proteins are secreted after proteolytic cleavage within the beta-amyloid peptide. The present investigation documents that, in cultured cells, amyloid precursor protein is cleaved on the plasma membrane by a membrane-bound endoprotease and that the specificity of peptide bond hydrolysis is largely independent of the primary sequence of the precursor.
Key findings
- Previous studies have established that amyloid precursor proteins are secreted after proteolytic cleavage within the beta-amyloid peptide.
- The present investigation documents that, in cultured cells, amyloid precursor protein is cleaved on the plasma membrane by a membrane-bound endoprotease and that the specificity of peptide bond hydrolysis is largely independent of the primary sequence of the precursor.
- The principal determinants of cleavage appear to be an alpha-helical conformation and the distance (12-13 residues) of the hydrolyzed bond from membrane.
Why it matters
In cultured cells, this study found that amyloid precursor protein is cleaved on the plasma membrane by a membrane-bound protease. It describes a basic mechanism of APP processing but does not test any treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 52/100
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 | 1992 — 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 740 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.6 citations a year over 36 year(s) since 1992 |
| 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 20 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 | 4 / 4 | Last-listed author Sangram S. Sisodia: h-index 101 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 1631093) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 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. Check the citation against the original before you use it.
APA 7th
Sisodia, S. S. (1992). Beta-amyloid precursor protein cleavage by a membrane-bound protease. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.89.13.6075
Vancouver
Sisodia SS. Beta-amyloid precursor protein cleavage by a membrane-bound protease. Proceedings of the National Academy of Sciences of the United States of America. 1992. doi:10.1073/pnas.89.13.6075. PMID: 1631093.
BibTeX
@article{sisodia1992-1631093,
author = {Sisodia, S. S.},
title = {{Beta-amyloid precursor protein cleavage by a membrane-bound protease}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1992},
doi = {10.1073/pnas.89.13.6075},
pmid = {1631093},
url = {https://doi.org/10.1073/pnas.89.13.6075}
}
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