ArticleProceedings of the National Academy of Sciences of the United States of America2012
Amyloid precursor protein (APP) traffics from the cell surface via endosomes for amyloid β (Aβ) production in the trans-Golgi network.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.
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Who cites it
138 citing papers in PubMed, 1 synthesis or guideline pooled it, 222 citations in OpenAlex.
- SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.PloS one · 2013Pooled it
- Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.Experimental & molecular medicine · 2026Review
- Molecular Glue Degraders Enhance CAPRIN1-Dependent Lysosomal Degradation of APP and Reduce Amyloid β in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Primary cilia-extracellular vesicle crosstalk in Alzheimer's disease: Emerging mechanisms and biomarker potential.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Persistent PirB cleavage drives Golgi-directed trafficking deficits underlying neurodegeneration.Translational neurodegeneration · 2026Article
- Functional relationships linking C99/APP-βCTF dimerization, proteostasis disruption, and organelle dysfunction.Cell communication and signaling : CCS · 2026Article
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- N-terminal modifications as fate switches in neurodegeneration: a mechanistic review.Frontiers in aging neuroscience · 2026Review
- APP E590D mutation increases generation of Aβ and Aη peptides and exacerbates tauopathy.NPJ dementia · 2026Article
- RABGAP1 is a sensor that facilitates the sorting and processing of amyloid precursor protein.The EMBO journal · 2025Article
- Negative interplay between HIV-1 Gag and amyloid precursor protein centers around competition for VPS4A and TSG101.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- APP lysine 612 lactylation ameliorates amyloid pathology and memory decline in Alzheimer's disease.The Journal of clinical investigation · 2025Article
- Vesicular trafficking and cell-cell communication in neurodevelopment and neurodegeneration.Frontiers in cell and developmental biology · 2025Review
- Potential Mechanisms of Tunneling Nanotube Formation and Their Role in Pathology Spread in Alzheimer's Disease and Other Proteinopathies.International journal of molecular sciences · 2024Review
- Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations.The Biochemical journal · 2024Review
- Unraveling the mechanistic interplay of mediators orchestrating the neuroprotective potential of harmine.Pharmacological reports : PR · 2024Review
- Comparison of plasma soluble and extracellular vesicles-associated biomarkers in Alzheimer's disease patients and cognitively normal individuals.Alzheimer's research & therapy · 2024Article
- Macrophages and Natural Killers Degrade α-Synuclein Aggregates.Molecular pharmaceutics · 2024Article
- Molecular Mechanisms Associated with Neurodegeneration of Neurotropic Viral Infection.Molecular neurobiology · 2024Review
78 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Amyloid precursor protein (APP) is processed sequentially by the β-site APP cleaving enzyme and γ-secretase to generate amyloid β (Aβ) peptides, one of the hallmarks of Alzheimer's disease. The intracellular location of Aβ production-endosomes or the trans-Golgi network (TGN)-remains uncertain. We investigated the role of different postendocytic trafficking events in Aβ(40) production using an RNAi approach. Depletion of Hrs and Tsg101, acting early in the multivesicular body pathway, retained APP in early endosomes and reduced Aβ(40) production. Conversely, depletion of CHMP6 and VPS4, acting late in the pathway, rerouted endosomal APP to the TGN for enhanced APP processing. We found that VPS35 (retromer)-mediated APP recycling to the TGN was required for efficient Aβ(40) production. An interruption of the bidirectional trafficking of APP between the TGN and endosomes, particularly retromer-mediated retrieval of APP from early endosomes to the TGN, resulted in the accumulation of endocytosed APP in early endosomes with reduced APP processing. These data suggest that Aβ(40) is generated predominantly in the TGN, relying on an endocytosed pool of APP recycled from early endosomes to the TGN.
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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.