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A novel pathway for amyloid precursor protein processing
Portelius E, Price E, Brinkmalm G, Brinkmalm G, Stiteler M, Olsson M, Persson R, Westman-Brinkmalm A et al.. Neurobiology of aging, 2009-07-14
Topic: Amyloid, tau and blood-test diagnosis
Amyloid precursor protein (APP) can be proteolytically processed along two pathways, the amyloidogenic that leads to the formation of the 40-42 amino acid long Alzheimer-associated amyloid β (Aβ) peptide and the non-amyloidogenic in which APP is cut in the middle of the Aβ domain thus precluding Aβ formation. Using immunoprecipitation and mass spectrometry we have shown that Aβ is present in cerebrospinal fluid (CSF) as several shorter isoforms in addition to Aβ1-40 and Aβ1-42. To address the question by which processing pathways these shorter isoforms arise, we have developed a cell model that accurately reflects the Aβ isoform pattern in CSF.
Key findings
- Using immunoprecipitation and mass spectrometry we have shown that Aβ is present in cerebrospinal fluid (CSF) as several shorter isoforms in addition to Aβ1-40 and Aβ1-42.
- To address the question by which processing pathways these shorter isoforms arise, we have developed a cell model that accurately reflects the Aβ isoform pattern in CSF.
- Using this model, we determined changes in the Aβ isoform pattern induced by α-, β-, and γ-secretase inhibitor treatment.
- All isoforms longer than and including Aβ1-17 were γ-secretase dependent whereas shorter isoforms were γ-secretase independent.
Why it matters
Amyloid-beta in spinal fluid is not only the familiar Aβ1-40 and Aβ1-42: this lab study used mass spectrometry to find "several shorter isoforms" as well. In a cell model built to mirror the spinal-fluid pattern, every isoform from Aβ1-17 upward depended on the enzyme γ-secretase, while shorter ones did not — pointing to a separate way these fragments are made. It is laboratory work on how amyloid is processed, not a test, treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 38/100
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, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 64 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| 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 | 2011 — 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 (OpenAlex dates this DOI to 2009, the record says 2011; OpenAlex values not used) — 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 | 3 / 6 | Cited by 12 other studies in this library |
| 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 19604603) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 64 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 24 of the 64 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Portelius, E., Price, E., Brinkmalm, G., Stiteler, M., Olsson, M., Persson, R., et al. (2011). A novel pathway for amyloid precursor protein processing. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2009.06.002
Vancouver
Portelius E, Price E, Brinkmalm G, Stiteler M, Olsson M, Persson R, et al. A novel pathway for amyloid precursor protein processing. Neurobiology of aging. 2011. doi:10.1016/j.neurobiolaging.2009.06.002. PMID: 19604603.
BibTeX
@article{portelius2011-19604603,
author = {Portelius, E. and Price, E. and Brinkmalm, G. and Stiteler, M. and Olsson, M. and Persson, R. and Westman-Brinkmalm, A. and others},
title = {{A novel pathway for amyloid precursor protein processing}},
journal = {Neurobiology of aging},
year = {2011},
doi = {10.1016/j.neurobiolaging.2009.06.002},
pmid = {19604603},
url = {https://doi.org/10.1016/j.neurobiolaging.2009.06.002}
}
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