ArticleStem cell reports2022
APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes.
Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 101 citations in OpenAlex.
- NTPDase2 suppresses hippocampal astrocyte-supplied cholesterol through hydrolyzing eATP in depression.Molecular psychiatry · 2026Article
- Traumatic Brain Injury and the Road to Alzheimer's Disease.Biomedicines · 2026Review
- Fibronectin mediates APOE4-driven blood-brain barrier dysfunction in Alzheimer's disease.Nature aging · 2026Article
- Review
- Human Stem Cell-Derived Models of the Alzheimer's Disease Neuroimmune System.International journal of molecular sciences · 2026Review
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- HDL-mimetic peptide treatment reverses APOE4-induced transcriptomic and lipidomic alterations in the brain of humanized APOE mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Association between serum lipid-apolipoprotein alterations and soluble syndecan-1 dynamics in sepsis: impact of apolipoprotein E isoforms.Biochemistry and biophysics reports · 2026Article
- The physiological effects of APOE genotype in healthy young/middle-aged individuals.Biological reviews of the Cambridge Philosophical Society · 2026Article
- Cortical Oscillations as an Endophenotype Mediating ApoE-ε2 Effects on Poststroke Functional Status.Stroke · 2026Article
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.PNAS nexus · 2026Article
- Lithium chloride suppresses ferroptosis of induced pluripotent stem cells with ApoE4/E4 from a sporadic Alzheimer's disease patient.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Astrocyte-blood-brain barrier crosstalk in cerebral small vessel disease: linking barrier dysfunction to neurovascular failure.Frontiers in neurology · 2026Review
- Dysfunction of lipid metabolism and lysosomal capacity: at the core of microglial aging?Frontiers in aging neuroscience · 2026Review
- Plasmalogen deficiency and the Alzheimer's disease risk of apolipoprotein E4.Brain communications · 2026Article
- Deciphering the role of APOE in cerebral amyloid angiopathy: from genetic insights to therapeutic horizons.Annals of medicine · 2025Review
- Investigating the Effects ofbioRxiv : the preprint server for biology · 2025Article
- APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons.bioRxiv : the preprint server for biology · 2025Article
- Dual inhibition of IRAK1/TAK1 signaling in astrocytes reduces accelerated mortality in human APOE4 knock-in APPswe/PSEN1dE9/P301S-Tau triple transgenic mouse model.Journal of neuroinflammation · 2025Article
- CRISPR-edited iPSCs reveal BSN gene mutations induce neuronal hyperexcitability via astrocyte lipid accumulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The apolipoprotein E4 (APOE4) variant is the strongest genetic risk factor for Alzheimer disease (AD), while the APOE2 allele is protective. A major question is how different APOE genotypes affect the physiology of astrocytes, the main APOE-producing brain cells. Here, we differentiated human APOE-isogenic induced pluripotent stem cells (iPSCs) (APOE4, E3, E2, and APOE knockout [APOE-KO]) to functional "iAstrocytes". Mass-spectrometry-based proteomic analysis showed genotype-dependent reductions of cholesterol and lipid metabolic and biosynthetic pathways (reduction: APOE4 >E3 >E2). Cholesterol efflux and biosynthesis were reduced in APOE4 iAstrocytes, while subcellular localization of cholesterol in lysosomes was elevated. An increase in immunoregulatory proteomic pathways (APOE4 >E3 >E2) was accompanied by elevated cytokine release in APOE4 cells (APOE4 >E3 >E2 >KO). Activation of iAstrocytes exacerbated proteomic changes and cytokine secretion mostly in APOE4 iAstrocytes, while APOE2 and APOE-KO iAstrocytes were least affected. Taken together, APOE4 iAstrocytes reveal a disease-relevant phenotype, causing dysregulated cholesterol/lipid homeostasis, increased inflammatory signaling, and reduced β-amyloid uptake, while APOE2 iAstrocytes show opposing effects.
Indexed as
Identifiers
What OpenQuestion holds
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.