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Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase
Steiner H, Fukumori A, Tagami S, Okochi M.. Cell stress, 2018-10-28
Topic: Brain proteins, microglia and lab models
Alzheimer´s disease (AD) is a devastating neurodegenerative disease of the elderly population. Genetic evidence strongly suggests that aberrant generation and/or clearance of the neurotoxic amyloid-β peptide (Aβ) is triggering the disease. Aβ is generated from the amyloid precursor protein (APP) by the sequential cleavages of β- and γ-secretase.
Key findings
- Genetic evidence strongly suggests that aberrant generation and/or clearance of the neurotoxic amyloid-β peptide (Aβ) is triggering the disease.
- Aβ is generated from the amyloid precursor protein (APP) by the sequential cleavages of β- and γ-secretase.
- The latter cleavage by γ-secretase, a unique and fascinating four-component protease complex, occurs in the APP transmembrane domain thereby releasing Aβ species of 37-43 amino acids in length including the longer, highly pathogenic peptides Aβ42 and Aβ43.
- The lack of a precise understanding of Aβ generation as well as of the functions of other γ-secretase substrates has been one factor underlying the disappointing failure of γ-secretase inhibitors in clinical trials, but on the other side also been a major driving force for structural and in depth mechanistic studies on this key AD drug target in the past few years.
Why it matters
This review describes how γ-secretase cuts amyloid precursor protein within its transmembrane domain to release amyloid β peptides of 37-43 amino acids, including the longer pathogenic forms. It is a summary of existing knowledge and does not itself provide a treatment, cure, or prevention.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 45/100
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 (Cell stress) |
| Journal's citation record | 0 / 4 | Cell Stress: journal h-index 38 (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 | 2 / 5 | 2018 — within 10 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 134 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.4 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 8.3× 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 36 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Masayasu Okochi: h-index 34 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Ludwig-Maximilians-Universität München: institution h-index 1,224 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31225454) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 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
Steiner, H., Fukumori, A., Tagami, S., & Okochi, M. (2018). Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase. Cell stress. https://doi.org/10.15698/cst2018.11.162
Vancouver
Steiner H, Fukumori A, Tagami S, Okochi M. Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase. Cell stress. 2018. doi:10.15698/cst2018.11.162. PMID: 31225454.
BibTeX
@article{steiner2018-31225454,
author = {Steiner, H. and Fukumori, A. and Tagami, S. and Okochi, M.},
title = {{Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase}},
journal = {Cell stress},
year = {2018},
doi = {10.15698/cst2018.11.162},
pmid = {31225454},
url = {https://doi.org/10.15698/cst2018.11.162}
}
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