ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 236 citations in OpenAlex.
- Article
- Integrative physiology of skeletal muscle for maintaining cognitive health.The Journal of physiology · 2026Review
- Exploring Gene Expression Patterns in Alzheimer's Disease Using a Human Microarray Data Meta-Analysis.Biology · 2026Article
- Characterization of endothelin-converting enzyme 1 as a key enzyme in the multienzyme Aβ degradation pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- New insights into the 17β-hydroxysteroid dehydrogenase type 10 and amyloid-β 42 derived cytotoxicity relevant to Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- The role of branched chain aminotransferase in the interrelated pathways of type 2 diabetes mellitus and Alzheimer's disease.Journal of diabetes and metabolic disorders · 2025Review
- Roles of the Receptor for Advanced Glycation End Products and Its Ligands in the Pathogenesis of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer's Disease Etiopathology.Antioxidants (Basel, Switzerland) · 2024Review
- The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases.Biomolecules · 2024Review
- Alzheimer's disease and its treatment-yesterday, today, and tomorrow.Frontiers in pharmacology · 2024Review
- Effects and mechanisms of APP and its cleavage product Aβ in the comorbidity of sarcopenia and Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging.Nature communications · 2023Article
- Amyloid precursor protein and its interacting proteins in neurodevelopment.Biochemical Society transactions · 2023Review
- APP family member dimeric complexes are formed predominantly in synaptic compartments.Cell & bioscience · 2023Article
- The Amyloid Precursor Protein Regulates Synaptic Transmission at Medial Perforant Path Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Differential effects of familial Alzheimer's disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity.Acta neuropathologica communications · 2023Article
- APP in the Neuromuscular Junction for the Development of Sarcopenia and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Effect of β-amyloid on blood-brain barrier properties and function.Biophysical reviews · 2023Review
- Reelin and APP Cooperatively Modulate Dendritic Spine FormationExperimental neurobiology · 2023Article
75 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
A critical role of the amyloid precursor protein (APP) in Alzheimer's disease (AD) pathogenesis has been well established. However, the physiological function of APP remains elusive and much debated. We reported previously that the APP family of proteins is essential in mediating the developing neuromuscular synapse. In the current study, we created a conditional allele of APP and deleted APP in presynaptic motor neuron or postsynaptic muscle. Crossing these alleles onto the APP-like protein 2-null background reveals that, unexpectedly, inactivating APP in either compartment results in neuromuscular synapse defects similar to the germline deletion and that postsynaptic APP is obligatory for presynaptic targeting of the high-affinity choline transporter and synaptic transmission. Using a HEK293 and primary hippocampus mixed-culture assay, we report that expression of APP in HEK293 cells potently promotes synaptogenesis in contacting axons. This activity is dependent on neuronal APP and requires both the extracellular and intracellular domains; the latter forms a complex with Mint1 and Cask and is replaceable by the corresponding SynCAM (synaptic cell adhesion molecule) sequences. These in vitro and in vivo studies identify APP as a novel synaptic adhesion molecule. We postulate that transsynaptic APP interaction modulates its synaptic function and that perturbed APP synaptic adhesion activity may contribute to synaptic dysfunction and AD pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.