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APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP
Weyer SW, Klevanski M, Delekate A, Voikar V, Aydin D, Hick M, Filippov M, Drost N et al.. The EMBO journal, 2011-04-26
Topic: Brain proteins, microglia and lab models
Despite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and its proteolytic fragments are still poorly understood. Previously, we generated APPsα knock-in (KI) mice expressing solely the secreted ectodomain APPsα. Here, we generated double mutants (APPsα-DM) by crossing APPsα-KI mice onto an APLP2-deficient background and show that APPsα rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice.
Key findings
- Previously, we generated APPsα knock-in (KI) mice expressing solely the secreted ectodomain APPsα.
- Here, we generated double mutants (APPsα-DM) by crossing APPsα-KI mice onto an APLP2-deficient background and show that APPsα rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice.
- Surviving APPsα-DM mice exhibited impaired neuromuscular transmission, with reductions in quantal content, readily releasable pool, and ability to sustain vesicle release that resulted in muscular weakness.
- We show that these defects may be due to loss of an APP/Mint2/Munc18 complex.
Why it matters
In mice, the secreted fragment APPsα was able to rescue most APP/APLP2 double knockout mice from death after birth, but surviving mice still had impaired nerve-to-muscle signaling and problems with learning and synaptic strengthening. These findings come from genetically modified animals and describe basic biology, not a treatment for people.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 (The EMBO journal) |
| Journal's citation record | 4 / 4 | The EMBO Journal: journal h-index 563 (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 | 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 | 5 / 7 | Cited 188 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.1 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 12.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 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 21522131) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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Read the original
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APA 7th
Weyer, S. W., Klevanski, M., Delekate, A., Voikar, V., Aydin, D., Hick, M., et al. (2011). APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP. The EMBO journal. https://doi.org/10.1038/emboj.2011.119
Vancouver
Weyer SW, Klevanski M, Delekate A, Voikar V, Aydin D, Hick M, et al. APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP. The EMBO journal. 2011. doi:10.1038/emboj.2011.119. PMID: 21522131.
BibTeX
@article{weyer2011-21522131,
author = {Weyer, S. W. and Klevanski, M. and Delekate, A. and Voikar, V. and Aydin, D. and Hick, M. and Filippov, M. and Drost, N. and others},
title = {{APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP}},
journal = {The EMBO journal},
year = {2011},
doi = {10.1038/emboj.2011.119},
pmid = {21522131},
url = {https://doi.org/10.1038/emboj.2011.119}
}
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