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A sensitive and quantitative assay for measuring cleavage of presenilin substrates
Karlström H, Bergman A, Lendahl U, Näslund J, Lundkvist J.. The Journal of biological chemistry, 2001-12-13
Topic: Brain proteins, microglia and lab models
The presenilin (PS) proteins are components of the gamma-secretase activity, which is central in the pathogenesis of Alzheimer's disease. Here we present a novel cell-based reporter gene assay for the quantification of PS-controlled gamma-secretase cleavage of the Alzheimer amyloid precursor protein (APP). We show that this assay offers several advantages, including increased sensitivity and specificity, improved quantification of cleavage, and simultaneous detection of all gamma-secretase cleavages in APP.
Key findings
- Here we present a novel cell-based reporter gene assay for the quantification of PS-controlled gamma-secretase cleavage of the Alzheimer amyloid precursor protein (APP).
- We show that this assay offers several advantages, including increased sensitivity and specificity, improved quantification of cleavage, and simultaneous detection of all gamma-secretase cleavages in APP.
- Furthermore, the APP assay can be used in parallel with a similar assay that records gamma-secretase cleavage of a Notch receptor.
- The use of these assays to analyze the effects of two known gamma-secretase inhibitors and postulated PS active site mutants on APP and Notch processing demonstrated that inhibitors and mutants that differently affect Notch and APP cleavage can be identified rapidly.
Why it matters
This work describes a new cell-based test for measuring gamma-secretase cleavage of the amyloid precursor protein, with greater sensitivity and specificity. It is a laboratory measurement tool and does not itself treat, cure, or prevent Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 39/100
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 | 2002 — 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 | 5 / 7 | Cited 105 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 3 / 6 | Cited 4.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Johan Lundkvist: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Karolinska Institutet: institution h-index 1,477 (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 11744687) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.c100649200
- PubMed: 11744687
- 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
Karlström, H., Bergman, A., Lendahl, U., Näslund, J., & Lundkvist, J. (2002). A sensitive and quantitative assay for measuring cleavage of presenilin substrates. The Journal of biological chemistry. https://doi.org/10.1074/jbc.c100649200
Vancouver
Karlström H, Bergman A, Lendahl U, Näslund J, Lundkvist J. A sensitive and quantitative assay for measuring cleavage of presenilin substrates. The Journal of biological chemistry. 2002. doi:10.1074/jbc.c100649200. PMID: 11744687.
BibTeX
@article{karlstrom2002-11744687,
author = {Karlström, H. and Bergman, A. and Lendahl, U. and Näslund, J. and Lundkvist, J.},
title = {{A sensitive and quantitative assay for measuring cleavage of presenilin substrates}},
journal = {The Journal of biological chemistry},
year = {2002},
doi = {10.1074/jbc.c100649200},
pmid = {11744687},
url = {https://doi.org/10.1074/jbc.c100649200}
}
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