ArticleHuman molecular genetics2017
APOE ε4/ε4 diminishes neurotrophic function of human iPSC-derived astrocytes.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 2 of them syntheses that pooled it.
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Who cites it
143 citing papers in PubMed, 2 syntheses or guidelines pooled it, 215 citations in OpenAlex.
- The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review.Frontiers in cellular neuroscience · 2022Pooled it
- A Hierarchical Framework for In Vitro Models of Alzheimer's Disease.WIREs mechanisms of diseasePooled it
- Review
- APOE3 and APOE4 human astrocytes differentially modulate Alzheimer's disease pathology and microglial responses in chimeric mice.Cell reports · 2026Article
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.PNAS nexus · 2026Article
- Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform.Journal of lipid research · 2026Article
- Modeling neurovascular dysfunction in Alzheimer's disease using an isogenic brain-chip model.Fluids and barriers of the CNS · 2026Article
- Astrocyte epigenetics in development, aging, and neurodegeneration: a DNA methylation perspective.Frontiers in molecular neuroscience · 2026Review
- Mechanisms, Mediators, and Pharmacological Approaches Targeting Brain Cholesterol Transport in Alzheimer's Disease.Current pharmaceutical design · 2026Review
- APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells.Frontiers in molecular biosciences · 2026Article
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- Compromised lipid metabolism, mitochondria respiration and neuroprotective effects in iPSC-derived astrocytes from a Smith-Lemli-Opitz syndrome patient.Human molecular genetics · 2025Article
- Astrocytes as Therapeutic Targets in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.bioRxiv : the preprint server for biology · 2025Article
- Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).International journal of molecular medicine · 2025Review
- A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.Molecular neurodegeneration · 2025Review
- Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype.Journal of neuroinflammation · 2025Article
- Lipid metabolism, remodelling and intercellular transfer in the CNS.Nature reviews. Neuroscience · 2025Review
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipids including cholesterol to support neuronal homeostasis and synaptic integrity. Although mouse models and corresponding primary cells have provided valuable tools for studying apoE isoform-dependent functions, recent studies have shown that human astrocytes have a distinct gene expression profile compare with rodent astrocytes. Human induced pluripotent stem cells (iPSCs) derived from individuals carrying specific gene variants or mutations provide an alternative cellular model more relevant to humans upon differentiation into specific cell types. Thus, we reprogramed human skin fibroblasts from cognitively normal individuals carrying APOE ε3/ε3 or ε4/ε4 genotype to iPSC clones and further differentiated them into neural progenitor cells and then astrocytes. We found that human iPSC-derived astrocytes secreted abundant apoE with apoE4 lipoprotein particles less lipidated compared to apoE3 particles. More importantly, human iPSC-derived astrocytes were capable of promoting neuronal survival and synaptogenesis when co-cultured with iPSC-derived neurons with APOE ε4/ε4 astrocytes less effective in supporting these neurotrophic functions than those with APOE ε3/ε3 genotype. Taken together, our findings demonstrate APOE genotype-dependent effects using human iPSC-derived astrocytes and provide novel evidence that the human iPSC-based model system is a strong tool to explore how apoE isoforms contribute to neurodegenerative diseases.
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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.