ArticleThe Journal of biological chemistry2011
Apolipoprotein E regulates the integrity of tight junctions in an isoform-dependent manner in an in vitro blood-brain barrier model.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 2 of them syntheses that pooled it.
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Who cites it
159 citing papers in PubMed, 2 syntheses or guidelines pooled it, 259 citations in OpenAlex.
- Impact of Apolipoprotein E4 on blood-brain barrier integrity in target replacement murine models: a systematic review and meta-analysis.Alzheimer's research & therapy · 2026Pooled it
- Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.Molecular neurobiology · 2016Pooled it
- Apolipoprotein E Plasma Concentrations Are Predictive of Recurrent Strokes: Insights From the SPARCL Trial.Journal of the American Heart Association · 2025Trial
- Depressive symptoms in chronic hepatitis C are associated with plasma apolipoprotein E deficiency.Metabolic brain disease · 2014Trial
- Review
- Promotion of hepatitis B virus infection by extracellular apolipoprotein E.Journal of virology · 2026Article
- Plasma Apolipoprotein E Levels and Adverse Clinical Outcomes After Ischemic Stroke.Journal of the American Heart Association · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Is there a role for apolipoprotein E in perinatal brain injury?Molecular and cellular pediatrics · 2026Review
- Construction of an In Vitro Blood-Brain Barrier Micro-Organoid Model Using Decellularized Squid Mantle Scaffold Film.Journal of functional biomaterials · 2026Article
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells.Frontiers in molecular biosciences · 2026Article
- The dual role of APOE ε4 allele in cerebral small vessel disease: independent genetic effects and effect modification of traditional risk factors.Frontiers in neurology · 2026Article
- Cortical layer multi-parameter analysis of neurovascular impairments in AD/ADRD rodent model with in vivo optical imaging.Translational neurodegeneration · 2025Article
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- Navigation Between Alzheimer's Disease (AD) and Its Various Pathophysiological Trajectories: The Pathogenic Link to Neuroimmunology-Genetics and Neuroinflammation.International journal of molecular sciences · 2025Review
- Immune cells in Alzheimer's disease: insights into pathogenesis and potential therapeutic targets.Medical review (2021) · 2025Review
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
- Endothelial progenitor cells and cerebral small vessel disease inCerebral circulation - cognition and behavior · 2025Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Apolipoprotein E (apoE) is a major apolipoprotein in the brain. The ε4 allele of apoE is a major risk factor for Alzheimer disease, and apoE deficiency in mice leads to blood-brain barrier (BBB) leakage. However, the effect of apoE isoforms on BBB properties are as yet unknown. Here, using an in vitro BBB model consisting of brain endothelial cells and pericytes prepared from wild-type (WT) mice, and primary astrocytes prepared from human apoE3- and apoE4-knock-in mice, we show that the barrier function of tight junctions (TJs) was impaired when the BBB was reconstituted with primary astrocytes from apoE4-knock-in mice (apoE4-BBB model). The phosphorylation of occludin at Thr residues and the activation of protein kinase C (PKC)η in mBECs were attenuated in the apoE4-BBB model compared with those in the apoE3-BBB model. The differential effects of apoE isoforms on the activation of PKCη, the phosphorylation of occludin at Thr residues, and TJ integrity were abolished following the treatment with an anti-low density lipoprotein receptor-related protein 1 (LRP1) antibody or a LRP1 antagonist receptor-associated protein. Consistent with the results of in vitro studies, BBB permeability was higher in apoE4-knock-in mice than in apoE3-knock-in mice. Our studies provide evidence that TJ integrity in BBB is regulated by apoE in an isoform-dependent manner.
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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.