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Acute function of secreted amyloid precursor protein fragment APPsα in synaptic plasticity
Hick M, Herrmann U, Weyer SW, Mallm JP, Tschäpe JA, Borgers M, Mercken M, Roth FC et al.. Acta neuropathologica, 2014-11-29
Topic: Brain proteins, microglia and lab models
The key role of APP in the pathogenesis of Alzheimer disease is well established. However, postnatal lethality of double knockout mice has so far precluded the analysis of the physiological functions of APP and the APLPs in the brain. Previously, APP family proteins have been implicated in synaptic adhesion, and analysis of the neuromuscular junction of constitutive APP/APLP2 mutant mice showed deficits in synaptic morphology and neuromuscular transmission.
Key findings
- However, postnatal lethality of double knockout mice has so far precluded the analysis of the physiological functions of APP and the APLPs in the brain.
- Previously, APP family proteins have been implicated in synaptic adhesion, and analysis of the neuromuscular junction of constitutive APP/APLP2 mutant mice showed deficits in synaptic morphology and neuromuscular transmission.
- Here, we generated animals with a conditional APP/APLP2 double knockout (cDKO) in excitatory forebrain neurons using NexCre mice.
- Electrophysiological recordings of adult NexCre cDKOs indicated a strong synaptic phenotype with pronounced deficits in the induction and maintenance of hippocampal LTP and impairments in paired pulse facilitation, indicating a possible presynaptic deficit.
Why it matters
Mice that lack both APP and its relative APLP2 die soon after birth, so until this study nobody could see what these Alzheimer's-linked proteins normally do in the adult brain. By removing both genes only in excitatory forebrain neurons, the researchers found that adult mice had "pronounced deficits in the induction and maintenance of hippocampal LTP", a lab measure of how nerve-cell connections strengthen, along with signs of "a possible presynaptic deficit." This is mouse research. It suggests APP-family proteins matter for normal synapse function, but it does not test any treatment in people.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (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 | 2015 — 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 188 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 9.4× 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 30 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ulrike Müller: h-index 60 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Heidelberg University: institution h-index 1,344 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25432317) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
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
Hick, M., Herrmann, U., Weyer, S. W., Mallm, J. P., Tschäpe, J. A., Borgers, M., et al. (2015). Acute function of secreted amyloid precursor protein fragment APPsα in synaptic plasticity. Acta neuropathologica. https://doi.org/10.1007/s00401-014-1368-x
Vancouver
Hick M, Herrmann U, Weyer SW, Mallm JP, Tschäpe JA, Borgers M, et al. Acute function of secreted amyloid precursor protein fragment APPsα in synaptic plasticity. Acta neuropathologica. 2015. doi:10.1007/s00401-014-1368-x. PMID: 25432317.
BibTeX
@article{hick2015-25432317,
author = {Hick, M. and Herrmann, U. and Weyer, S. W. and Mallm, J. P. and Tschäpe, J. A. and Borgers, M. and Mercken, M. and Roth, F. C. and others},
title = {{Acute function of secreted amyloid precursor protein fragment APPsα in synaptic plasticity}},
journal = {Acta neuropathologica},
year = {2015},
doi = {10.1007/s00401-014-1368-x},
pmid = {25432317},
url = {https://doi.org/10.1007/s00401-014-1368-x}
}
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