ArticlePloS one2015
The Amyloid Precursor Protein Controls PIKfyve Function.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Sex- and brain region-specific gene expression in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Developmental and Age-Related RAB-3 phenotypes in amicroPublication biology · 2026Article
- Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer's disease.Cell reports. Medicine · 2024Article
- The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system.Journal of cell science · 2023Article
- Biomembrane-Derived Nanoparticles in Alzheimer's Disease Therapy: A Comprehensive Review of Synthetic Lipid Nanoparticles and Natural Cell-Derived Vesicles.International journal of nanomedicine · 2023Review
- Liposome based drug delivery as a potential treatment option for Alzheimer's disease.Neural regeneration research · 2022Review
- Modeling Alzheimer's Disease inBiomedicines · 2022Review
- Ultrastructural and dynamic studies of the endosomal compartment in Down syndrome.Acta neuropathologica communications · 2020Article
- The PIKfyve complex regulates the early melanosome homeostasis required for physiological amyloid formation.Journal of cell science · 2019Article
- Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes.Frontiers in neuroscience · 2019Article
- Human genetic variation inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- APP as a Protective Factor in Acute Neuronal Insults.Frontiers in molecular neuroscience · 2017Review
- A cell-permeable tool for analysing APP intracellular domain function and manipulation of PIKfyve activity.Bioscience reports · 2016Article
- PIKfyve activity is required for lysosomal trafficking of tau aggregates and tau seeding.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
While the Amyloid Precursor Protein (APP) plays a central role in Alzheimer's disease, its cellular function still remains largely unclear. It was our goal to establish APP function which will provide insights into APP's implication in Alzheimer's disease. Using our recently developed proteo-liposome assay we established the interactome of APP's intracellular domain (known as AICD), thereby identifying novel APP interactors that provide mechanistic insights into APP function. By combining biochemical, cell biological and genetic approaches we validated the functional significance of one of these novel interactors. Here we show that APP binds the PIKfyve complex, an essential kinase for the synthesis of the endosomal phosphoinositide phosphatidylinositol-3,5-bisphosphate. This signalling lipid plays a crucial role in endosomal homeostasis and receptor sorting. Loss of PIKfyve function by mutation causes profound neurodegeneration in mammals. Using C. elegans genetics we demonstrate that APP functionally cooperates with PIKfyve in vivo. This regulation is required for maintaining endosomal and neuronal function. Our findings establish an unexpected role for APP in the regulation of endosomal phosphoinositide metabolism with dramatic consequences for endosomal biology and important implications for our understanding of Alzheimer's disease.
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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.