Home › Research › Biomarkers
When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease
Wolfe MS.. EMBO reports, 2007-02-01
Topic: Disease mechanisms in lab and animal studies
More than 100 missense mutations in presenilin 1 and 2 are associated with early-onset dominant Alzheimer disease. These proteins span the membrane several times and are ostensibly the catalytic component of the gamma-secretase complex, which is responsible for producing the amyloid beta-peptide (Abeta) that deposits in the Alzheimer brain. A common outcome of Alzheimer-associated presenilin mutations is an increase in the ratio of the more aggregation-prone 42-residue form of Abeta to the 40-residue variant, which is often referred to as a presenilin 'gain of function'. An apparent paradox is that most of these mutant presenilins have reduced proteolytic efficiency, which forms part of the counter argument that presenilin 'loss of function' can cause the neuronal dysfunction and death that lead to the disease. In this review, a unifying hypothesis is presented that puts forward a biochemical mechanism by which slower less-efficient forms of the protease can result in a greater proportion of 42-residue Abeta.
Key findings
- More than 100 missense mutations in presenilin 1 and 2 are associated with early-onset dominant Alzheimer disease.
- In this review, a unifying hypothesis is presented that puts forward a biochemical mechanism by which slower less-efficient forms of the protease can result in a greater proportion of 42-residue Abeta.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Evidence strengthLow
How this study scored 36/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (EMBO reports) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2007 — within 20 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17268504) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Wolfe, M. S. (2007). When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO reports. https://doi.org/10.1038/sj.embor.7400896
Vancouver
Wolfe MS. When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO reports. 2007. doi:10.1038/sj.embor.7400896. PMID: 17268504.
BibTeX
@article{wolfe2007-17268504,
author = {Wolfe, M. S.},
title = {{When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease}},
journal = {EMBO reports},
year = {2007},
doi = {10.1038/sj.embor.7400896},
pmid = {17268504},
url = {https://doi.org/10.1038/sj.embor.7400896}
}