ArticlePloS one2014
APP is cleaved by Bace1 in pre-synaptic vesicles and establishes a pre-synaptic interactome, via its intracellular domain, with molecular complexes that regulate pre-synaptic vesicles functions.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Presynaptic accumulation of APP-CTFβ may contribute to synaptic dysfunction in Alzheimer's disease.The EMBO journal · 2026Article
- The exocyst is an insulin-sensitive regulator of amyloid precursor protein trafficking and amyloid-beta generation in neurons.bioRxiv : the preprint server for biology · 2026Article
- Levetiracetam prevents Aβ production through SV2a-dependent modulation of APP processing in Alzheimer's disease models.Science translational medicine · 2026Article
- Amyloid-β disrupts APP-regulated protein aggregation and dissociation from recycling endosomal membranes.The EMBO journal · 2025Article
- Lysosomal dysfunction in Down syndrome and Alzheimer mouse models is caused by v-ATPase inhibition by TyrScience advances · 2023Article
- The Cleavage-Specific Tau 12A12mAb Exerts an Anti-Amyloidogenic Action by Modulating the Endocytic and Bioenergetic Pathways in Alzheimer's Disease Mouse Model.International journal of molecular sciences · 2023Article
- Review
- Knockdown of Amyloid Precursor Protein Increases Ion Channel Expression and Alters CaInternational journal of molecular sciences · 2023Article
- Crosstalk of copper and zinc in the pathogenesis of vascular dementia.Journal of clinical biochemistry and nutrition · 2022Article
- PTPRD and DCC Are Novel BACE1 Substrates Differentially Expressed in Alzheimer's Disease: A Data Mining and Bioinformatics Study.International journal of molecular sciences · 2022Article
- Late-long-term potentiation magnitude, but not Aβ levels and amyloid pathology, is associated with behavioral performance in a rat knock-in model of Alzheimer disease.Frontiers in aging neuroscience · 2022Article
- Pulse-Chase Proteomics of the App Knockin Mouse Models of Alzheimer's Disease Reveals that Synaptic Dysfunction Originates in Presynaptic Terminals.Cell systems · 2021Article
- MicrogliaeLife · 2020Article
- Amyloid, APP, and Electrical Activity of the Brain.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2020Review
- Amyloids: Regulators of Metal Homeostasis in the Synapse.Molecules (Basel, Switzerland) · 2020Review
- Article
- Proximity ligation assay reveals both pre- and postsynaptic localization of the APP-processing enzymes ADAM10 and BACE1 in rat and human adult brain.BMC neuroscience · 2020Article
- Intracellular Trafficking Mechanisms of Synaptic Dysfunction in Alzheimer's Disease.Frontiers in cellular neuroscience · 2020Article
- Facilitation of glutamate, but not GABA, release in Familial Alzheimer's APP mutant Knock-in rats with increased β-cleavage of APP.Aging cell · 2019Article
- Tuning of Glutamate, But Not GABA, Release by an Intrasynaptic Vesicle APP Domain Whose Function Can Be Modulated by β- or α-Secretase Cleavage.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Amyloid Precursor Protein (APP) is a type I membrane protein that undergoes extensive processing by secretases, including BACE1. Although mutations in APP and genes that regulate processing of APP, such as PSENs and BRI2/ITM2B, cause dementias, the normal function of APP in synaptic transmission, synaptic plasticity and memory formation is poorly understood. To grasp the biochemical mechanisms underlying the function of APP in the central nervous system, it is important to first define the sub-cellular localization of APP in synapses and the synaptic interactome of APP. Using biochemical and electron microscopy approaches, we have found that APP is localized in pre-synaptic vesicles, where it is processed by Bace1. By means of a proteomic approach, we have characterized the synaptic interactome of the APP intracellular domain. We focused on this region of APP because in vivo data underline the central functional and pathological role of the intracellular domain of APP. Consistent with the expression of APP in pre-synaptic vesicles, the synaptic APP intracellular domain interactome is predominantly constituted by pre-synaptic, rather than post-synaptic, proteins. This pre-synaptic interactome of the APP intracellular domain includes proteins expressed on pre-synaptic vesicles such as the vesicular SNARE Vamp2/Vamp1 and the Ca2+ sensors Synaptotagmin-1/Synaptotagmin-2, and non-vesicular pre-synaptic proteins that regulate exocytosis, endocytosis and recycling of pre-synaptic vesicles, such as target-membrane-SNAREs (Syntaxin-1b, Syntaxin-1a, Snap25 and Snap47), Munc-18, Nsf, α/β/γ-Snaps and complexin. These data are consistent with a functional role for APP, via its carboxyl-terminal domain, in exocytosis, endocytosis and/or recycling of pre-synaptic vesicles.
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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.