ArticleCell reports2020
PICALM Rescues Endocytic Defects Caused by the Alzheimer's Disease Risk Factor APOE4.
Article in Cell reports, 2020. 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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Who cites it
60 citing papers in PubMed.
- APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.Nature communications · 2026Article
- Article
- BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.American journal of physiology. Cell physiology · 2026Article
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.PNAS nexus · 2026Article
- Article
- BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.bioRxiv : the preprint server for biology · 2025Article
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.bioRxiv : the preprint server for biology · 2025Article
- Review
- Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype.Journal of neuroinflammation · 2025Article
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- The Cross-Talk Between the Peripheral and Brain Cholesterol Metabolisms.Current issues in molecular biology · 2025Review
- Regulatory Mechanisms and Therapeutic Implications of Lysosomal Dysfunction in Alzheimer's Disease.International journal of biological sciences · 2025Review
- Insights into targeted ferroptosis in mechanisms, biology, and role of Alzheimer's disease: an update.Frontiers in aging neuroscience · 2025Review
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.PLoS computational biology · 2024Article
- Recent Advances in Therapeutics for the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2024Review
- Exploring the Dynamic Changes of Brain Lipids, Lipid Rafts, and Lipid Droplets in Aging and Alzheimer's Disease.Biomolecules · 2024Review
- Coupling of Alzheimer's Disease Genetic Risk Factors with Viral Susceptibility and Inflammation.Aging and disease · 2024Review
- PICALM as a Novel Prognostic Biomarker and Its Correlation with Immune Infiltration in Breast Cancer.Applied biochemistry and biotechnology · 2024Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
The ε4 allele of apolipoprotein E (APOE4) is a genetic risk factor for many diseases, including late-onset Alzheimer's disease (AD). We investigate the cellular consequences of APOE4 in human iPSC-derived astrocytes, observing an endocytic defect in APOE4 astrocytes compared with their isogenic APOE3 counterparts. Given the evolutionarily conserved nature of endocytosis, we built a yeast model to identify genetic modifiers of the endocytic defect associated with APOE4. In yeast, only the expression of APOE4 results in dose-dependent defects in both endocytosis and growth. We discover that increasing expression of the early endocytic adaptor protein Yap1802p, a homolog of the human AD risk factor PICALM, rescues the APOE4-induced endocytic defect. In iPSC-derived human astrocytes, increasing expression of PICALM similarly reverses endocytic disruptions. Our work identifies a functional interaction between two AD genetic risk factors-APOE4 and PICALM-centered on the conserved biological process of endocytosis.
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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.