ArticleEMBO reports2020
AP-2 reduces amyloidogenesis by promoting BACE1 trafficking and degradation in neurons.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- Salidroside mitigates cognitive deficits in AlClFrontiers in behavioral neuroscience · 2026Article
- Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.bioRxiv : the preprint server for biology · 2025Article
- AP2A1 activates Rab7 to promote axonal autophagosome transport and slow the progression of Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Neurons Specialize in Presynaptic Autophagy: A Perspective to Ameliorate Neurodegeneration.Molecular neurobiology · 2025Review
- Autophagy in alzheimer disease pathogenesis and its therapeutic values.Autophagy reports · 2025Review
- 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
- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Autophagy initiation triggers p150Cellular and molecular life sciences : CMLS · 2024Article
- The AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors.Life science alliance · 2024Article
- The role of autophagy in Parkinson's disease: a gender difference overview.Frontiers in pharmacology · 2024Review
- 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
- Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer's disease.BMC medicine · 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
- Transcriptomic Profiling Reveals Discrete Poststroke Dementia Neuronal and Gliovascular Signatures.Translational stroke research · 2023Article
- APP and Bace1: Differential effect of cholesterol enrichment on processing and plasma membrane mobility.iScience · 2023Article
- AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.Traffic (Copenhagen, Denmark) · 2023Article
- Expression of the human herpesvirus 6A latency-associated transcript U94A impairs cytoskeletal functions in human neural cells.Molecular and cellular neurosciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Cleavage of amyloid precursor protein (APP) by BACE-1 (β-site APP cleaving enzyme 1) is the rate-limiting step in amyloid-β (Aβ) production and a neuropathological hallmark of Alzheimer's disease (AD). Despite decades of research, mechanisms of amyloidogenic APP processing remain highly controversial. Here, we show that in neurons, APP processing and Aβ production are controlled by the protein complex-2 (AP-2), an endocytic adaptor known to be required for APP endocytosis. Now, we find that AP-2 prevents amyloidogenesis by additionally functioning downstream of BACE1 endocytosis, regulating BACE1 endosomal trafficking and its delivery to lysosomes. AP-2 is decreased in iPSC-derived neurons from patients with late-onset AD, while conditional AP-2 knockout (KO) mice exhibit increased Aβ production, resulting from accumulation of BACE1 within late endosomes and autophagosomes. Deletion of BACE1 decreases amyloidogenesis and mitigates synapse loss in neurons lacking AP-2. Taken together, these data suggest a mechanism for BACE1 intracellular trafficking and degradation via an endocytosis-independent function of AP-2 and reveal a novel role for endocytic proteins in AD.
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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.