Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2
Open accessAbstract
Biochemical and genetic studies place the amyloid precursor protein (APP) at the center stage of Alzheimer's disease (AD) pathogenesis. Although mutations in the APP gene lead to dominant inheritance of familial AD, the normal function of APP remains elusive. Here, we report that the APP family of proteins plays an essential role in the development of neuromuscular synapses. Mice deficient in APP and its homolog APP-like protein 2 (APLP2) exhibit aberrant apposition of presynaptic marker proteins with postsynaptic acetylcholine receptors and excessive nerve terminal sprouting. The number of synaptic vesicles at presynaptic terminals is dramatically reduced. These structural abnormalities are accompanied by defective neurotransmitter release and a high incidence of synaptic failure. Our results identify APP/APLP2 as key regulators of structure and function of developing neuromuscular synapses.
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APP/APP-like protein 2 double-KO mice exhibit defective neuromuscular junctions, excessive nerve terminal sprouting, and defective synaptic transmission.
“APP/APP-like protein 2 double-KO mice exhibit defective neuromuscular junctions, excessive nerve terminal sprouting, and defective synaptic transmission [47].”
From FMRP Mediates mGluR5-Dependent Translation of Amyloid Precursor Protein (2007) · cites this paper as [47]
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“]. APP/APP-like protein 2 double-KO mice exhibit defective neuromuscular junctions, excessive nerve terminal sprouting, and defective synaptic transmission [”
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- Authors
- Wang, P., Yang, G., Mosier, D. R., Chang, P., Zaidi, T., Gong, Y.-D., Zhao, N.-M., Dominguez, B., Lee, K.-F., Gan, W.-B., & Zheng, H.
- Affiliations
- Baylor College of Medicine (US)
- Tsinghua University (CN)
- New York University (US)
- Salk Institute for Biological Studies (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-02-02
- Volume
- 25
- Issue
- 5
- Pages
- 1219-1225
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725967
- OpenAlex
- W2130763296
- Cited by
- 290
- References
- 4
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 16 · 2022: 8 · 2021: 12 · 2020: 5 · 2019: 9 · 2018: 8 · 2017: 14 · 2016: 15 · 2015: 13 · 2014: 18 · 2013: 18 · 2012: 20
- FWCI
- 12.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- Alzheimer's Association
- National Institutes of Health
- National Institute on Aging (AG20670, R01AG021141, AG21141, R01AG020670)
- National Institute of Neurological Disorders and Stroke (NS40039, R01NS041846, NS041846, R01NS040039)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid precursor protein, synaptic structure, acetylcholine receptor, synaptic vesicles, neurotransmitter release, synaptic failure, APP knockout mice, Alzheimer's disease
- MeSH terms
- Animals, Animals, Newborn, Diaphragm, Mice, Neurologic Mutants, Motor Endplate, Muscle Proteins, Neck Muscles, Synaptic Transmission, Neuromuscular Junction, Phenotype, Receptors, Cholinergic, Synaptic Vesicles, Biomarkers, Amyloid beta-Protein Precursor, Receptors, Presynaptic, Mice, Knockout, Mice
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