ArticleNeurobiology of disease2011
Retromer disruption promotes amyloidogenic APP processing.
Article in Neurobiology of disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 96 citations in OpenAlex.
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- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- RABGAP1 is a sensor that facilitates the sorting and processing of amyloid precursor protein.The EMBO journal · 2025Article
- γ-secretase facilitates retromer-mediated retrograde transport.Journal of cell science · 2025Article
- Exploring Therapeutic Strategies: The Relationship between Metabolic Disorders and FOXO Signalling in Alzheimer's Disease.CNS & neurological disorders drug targets · 2025Review
- γ-secretase facilitates retromer-mediated retrograde transport.bioRxiv : the preprint server for biology · 2024Article
- Apolipoprotein E2 Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging.Traffic (Copenhagen, Denmark) · 2024Article
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- Chronic nSMase inhibition suppresses neuronal exosome spreading and sex-specifically attenuates amyloid pathology in APP knock-in Alzheimer's disease mice.Neurobiology of disease · 2023Article
- Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health.Nature communications · 2023Article
- Receptor Recycling by Retromer.Molecular and cellular biology · 2023Review
- Retromer deficiency in Tauopathy models enhances the truncation and toxicity of Tau.Nature communications · 2022Article
- The understudied links of the retromer complex to age-related pathways.GeroScience · 2022Article
- An Update on Coat Protein Complexes for Vesicle Formation in Plant Post-Golgi Trafficking.Frontiers in plant science · 2022Review
- Implications of exosomes derived from cholesterol-accumulated astrocytes in Alzheimer's disease pathology.Disease models & mechanisms · 2021Article
- Extracellular Vesicles for the Diagnosis and Treatment of Parkinson's Disease.Aging and disease · 2021Review
- Opposing functions for retromer and Rab11 in extracellular vesicle traffic at presynaptic terminals.The Journal of cell biology · 2021Article
- Retromer dysfunction at the nexus of tauopathies.Cell death and differentiation · 2021Review
- Function of exosomes in neurological disorders and brain tumors.Extracellular vesicles and circulating nucleic acids · 2021Article
- Overdosing on iron: Elevated iron and degenerative brain disorders.Experimental biology and medicine (Maywood, N.J.) · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Retromer deficiency has been implicated in sporadic AD and animals deficient in retromer components exhibit pronounced neurodegeneration. Because retromer performs retrograde transport from the endosome to the Golgi apparatus and neuronal Aβ is found in late endosomal compartments, we speculated that retromer malfunction might enhance amyloidogenic APP processing by promoting interactions between APP and secretase enzymes in late endosomes. We have evaluated changes in amyloid precursor protein (APP) processing and trafficking as a result of disrupted retromer activity by knockdown of Vps35, a vacuolar sorting protein that is an essential component of the retromer complex. Knocking down retromer activity produced no change in the quantity or cellular distribution of total cellular APP and had no affect on internalization of cell-surface APP. Retromer deficiency did, however, increase the ratio of secreted Aβ42:Aβ40 in HEK-293 cells over-expressing APP695, due primarily to a decrease in Aβ40 secretion. Recent studies suggest that the retromer-trafficked protein, Wntless, is secreted at the synapse in exosome vesicles and that these same vesicles contain Aβ. We therefore hypothesized that retromer deficiency may be associated with altered exosomal secretion of APP and/or secretase fragments. Holo-APP, Presenilin and APP C-terminal fragments were detected in exosomal vesicles secreted from HEK-293 cells. Levels of total APP C-terminal fragments were significantly increased in exosomes secreted by retromer deficient cells. These data suggest that reduced retromer activity can mimic the effects of familial AD Presenilin mutations on APP processing and promote export of amyloidogenic APP derivatives.
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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.