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The amyloid precursor protein: a biochemical enigma in brain development, function and disease
Nalivaeva NN, Turner AJ.. FEBS letters, 2013-05-16
Topic: Brain proteins, microglia and lab models
For 20 years the amyloid cascade hypothesis of Alzheimer disease (AD) has placed the amyloid-β peptide (Aβ), formed from the amyloid precursor protein (APP), centre stage in the process of neurodegeneration. However, no new therapeutic agents have reached the clinic through exploitation of the hypothesis. The APP metabolites, including Aβ, generated by its proteolytic processing, have distinct physiological functions.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Nalivaeva, N. N., & Turner, A. J. (2013). The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS letters. https://doi.org/10.1016/j.febslet.2013.05.010
Vancouver
Nalivaeva NN, Turner AJ. The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS letters. 2013. doi:10.1016/j.febslet.2013.05.010. PMID: 23684647.
BibTeX
@article{nalivaeva2013-23684647,
author = {Nalivaeva, N. N. and Turner, A. J.},
title = {{The amyloid precursor protein: a biochemical enigma in brain development, function and disease}},
journal = {FEBS letters},
year = {2013},
doi = {10.1016/j.febslet.2013.05.010},
pmid = {23684647},
url = {https://doi.org/10.1016/j.febslet.2013.05.010}
}
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.
Key findings
- However, no new therapeutic agents have reached the clinic through exploitation of the hypothesis.
- The APP metabolites, including Aβ, generated by its proteolytic processing, have distinct physiological functions.
- In particular, the cleaved intracellular domain of APP (AICD) regulates expression of several genes, including APP itself, the β-secretase BACE-1 and the Aβ-degrading enzyme, neprilysin and this transcriptional regulation involves direct promoter binding of AICD.
- Of the three major splice isoforms of APP (APP695, APP751, APP770), APP695 is the predominant neuronal form, from which Aβ and transcriptionally-active AICD are preferentially generated by selective processing through the amyloidogenic pathway.
Why it matters
This review points out that no new therapeutic agents have reached the clinic through the amyloid cascade hypothesis, and that APP metabolites including beta-amyloid have distinct physiological functions, with the intracellular domain regulating several genes. It is a discussion of the complexity of APP biology rather than a report of a working treatment.
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 (FEBS letters) |
| Journal's citation record | 3 / 4 | FEBS Letters: journal h-index 393 (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 | 2013 — 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 | 5 / 7 | Cited 273 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.2 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 19.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 42 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Anthony J. Turner: h-index 80 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Leeds: institution h-index 950 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23684647) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.febslet.2013.05.010
- PubMed: 23684647
- Original source →
- Free full text: FEBS Letters →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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