ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
Differential Signaling Mediated by ApoE2, ApoE3, and ApoE4 in Human Neurons Parallels Alzheimer's Disease Risk.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 4 of them syntheses that pooled it.
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Who cites it
92 citing papers in PubMed, 4 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer's Disease and MCI: A Review.International journal of molecular sciences · 2023Pooled it
- The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review.Frontiers in cellular neuroscience · 2022Pooled it
- Regulation of autophagy, lipid metabolism, and neurodegenerative pathology by heparan sulfate proteoglycans.Frontiers in genetics · 2022Pooled it
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- TREM2 in neurodegeneration and diseases.Molecular psychiatry · 2026Review
- Aortic Single-Cell Transcriptome Analysis Reveals ApoE-Isoform-Specific Influences on Vascular Disease.International journal of molecular sciences · 2026Article
- Beyond Lipidation: CSF APOE4 Protein Burden, Not HDL Subclass, Drives Tau Associations in APOE4 Alzheimer's Disease.Research square · 2026Article
- The apolipoprotein gene: a modulating role on brain volume and cognitive function in carriers of the fragile X premutation.Neurobiology of disease · 2026Article
- Group 1 mGluR stimulation rescues APOE4-mediated translation defects in neurons.Life science alliance · 2026Article
- Association between apolipoprotein E gene polymorphisms and the effects of high-intensity interval training on body composition in university students.Frontiers in nutrition · 2026Article
- ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer's Disease Pathogenesis.Biochemistry · 2025Article
- Axon Regeneration and Functional Recovery after Spinal Cord Injury is Enhanced by Allele-Specific ApoE Neuronal Action through LRP8.bioRxiv : the preprint server for biology · 2025Article
- APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids.Stem cell reports · 2025Article
- Apolipoprotein E selectively supports gammaherpesvirus replication in macrophages.Journal of virology · 2025Article
- Concentrations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury in men in different apolipoprotein E phenotypes.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- APOE genotype determines cell-type-specific pathological landscape of Alzheimer's disease.Neuron · 2025Article
- ApoE4 requires lipidation enhancement to resolve cellular lipid and protein abnormalities following NPC1 inhibition.Scientific reports · 2025Article
- Multi-Omics Approach Reveals Genes and Pathways Affected in Miller-Dieker Syndrome.Molecular neurobiology · 2025Article
- Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype.Aging cell · 2025Article
32 more citing papers are in PubMed but not listed here.
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5 authors at 2 institutions in 2 countries.
Funding
Abstract
In blood, apolipoprotein E (ApoE) is a component of circulating lipoproteins and mediates the clearance of these lipoproteins from blood by binding to ApoE receptors. Humans express three genetic ApoE variants, ApoE2, ApoE3, and ApoE4, which exhibit distinct ApoE receptor-binding properties and differentially affect Alzheimer's disease (AD), such that ApoE2 protects against, and ApoE4 predisposes to AD. In brain, ApoE-containing lipoproteins are secreted by activated astrocytes and microglia, but their functions and role in AD pathogenesis are largely unknown. Ample evidence suggests that ApoE4 induces microglial dysregulation and impedes Aβ clearance in AD, but the direct neuronal effects of ApoE variants are poorly studied. Extending previous studies, we here demonstrate that the three ApoE variants differentially activate multiple neuronal signaling pathways and regulate synaptogenesis. Specifically, using human neurons (male embryonic stem cell-derived) cultured in the absence of glia to exclude indirect glial mechanisms, we show that ApoE broadly stimulates signal transduction cascades. Among others, such stimulation enhances APP synthesis and synapse formation with an ApoE4>ApoE3>ApoE2 potency rank order, paralleling the relative risk for AD conferred by these ApoE variants. Unlike the previously described induction of
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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 Socratic graph.