ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Direct Transcriptional Effects of Apolipoprotein E.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- 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 Relationship Between Adverse Childhood Experiences and Alzheimer's Disease: A Systematic Review.Frontiers in aging neuroscience · 2022Pooled it
- Apolipoprotein E (APOE) Promotes Cell Proliferation and Invasion in Glioma via the PI3K/AKT Signaling Pathway.Cancer management and research · 2026Article
- Short-Term Changes in Depressive Symptoms Among Patients with Alzheimer's Disease Following a Precision Medicine Intervention.Brain sciences · 2025Article
- Proteome-Based Biomarkers for Alzheimer's Disease: Old Acquisitions and Innovative Proposals.International journal of molecular sciences · 2025Review
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
- Article
- The multifaceted roles of apolipoprotein E4 in Alzheimer's disease pathology and potential therapeutic strategies.Cell death discovery · 2025Review
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
- Age-related changes in the proteome and mitochondrial metabolism of rabbit adipose-derived stromal/stem cells.Scientific reports · 2025Article
- Discovery of an ApoE4-targeted small-molecule SirT1 enhancer for the treatment of Alzheimer's disease.Scientific reports · 2025Article
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.PLoS computational biology · 2024Article
- Reduction of APOE accounts for neurobehavioral deficits in fetal alcohol spectrum disorders.Molecular psychiatry · 2024Article
- Readdressing the Localization of Apolipoprotein E (APOE) in Mitochondria-Associated Endoplasmic Reticulum (ER) Membranes (MAMs): An Investigation of the Hepatic Protein-Protein Interactions of APOE with the Mitochondrial Proteins Lon Protease (LONP1), Mitochondrial Import Receptor Subunit TOM40 (TOMM40) and Voltage-Dependent Anion-Selective Channel 1 (VDAC1).International journal of molecular sciences · 2024Article
- Insights into the roles of Apolipoprotein E in adipocyte biology and obesity.International journal of obesity (2005) · 2024Review
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.bioRxiv : the preprint server for biology · 2024Article
- APOE-NOTCH axis governs elastogenesis during human cardiac valve remodeling.Nature cardiovascular research · 2024Article
- APOLIPOPROTEIN E GENE POLYMORPHISMS AND PLASMA LIPIDS IN PERSONS LIVING WITH HIV: A CROSS SECTIONAL STUDY.Annals of Ibadan postgraduate medicine · 2024Article
- Article
- Neuronal Stem Cells from Late-Onset Alzheimer Patients Show Altered Regulation of Sirtuin 1 Depending on Apolipoprotein E Indicating Disturbed Stem Cell Plasticity.Molecular neurobiology · 2024Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A major unanswered question in biology and medicine is the mechanism by which the product of the apolipoprotein E ε4 allele, the lipid-binding protein apolipoprotein E4 (ApoE4), plays a pivotal role in processes as disparate as Alzheimer's disease (AD; in which it is the single most important genetic risk factor), atherosclerotic cardiovascular disease, Lewy body dementia, hominid evolution, and inflammation. Using a combination of neural cell lines, skin fibroblasts from AD patients, and ApoE targeted replacement mouse brains, we show in the present report that ApoE4 undergoes nuclear translocation, binds double-stranded DNA with high affinity (low nanomolar), and functions as a transcription factor. Using chromatin immunoprecipitation and high-throughput DNA sequencing, our results indicate that the ApoE4 DNA binding sites include ∼1700 gene promoter regions. The genes associated with these promoters provide new insight into the mechanism by which AD risk is conferred by ApoE4, because they include genes associated with trophic support, programmed cell death, microtubule disassembly, synaptic function, aging, and insulin resistance, all processes that have been implicated in AD pathogenesis. Significance statement: This study shows for the first time that apolipoprotein E4 binds DNA with high affinity and that its binding sites include 1700 promoter regions that include genes associated with neurotrophins, programmed cell death, synaptic function, sirtuins and aging, and insulin resistance, all processes that have been implicated in Alzheimer's disease pathogenesis.
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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.