ArticleBrain : a journal of neurology2022
APOE4 derived from astrocytes leads to blood-brain barrier impairment.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06881225 (Study on the Regulation of Blood-Brain Barrier Permeability by APOE Gene Polymorphism and Its Impact on Cognitive Function After Radiotherapy for Nasopharyngeal Carcinoma), which is not on this map. Cited by 134 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.
Study on the Regulation of Blood-Brain Barrier Permeability by APOE Gene Polymorphism and Its Impact on Cognitive Function After Radiotherapy for Nasopharyngeal Carcinoma: An MRI Investigation
Who cites it
134 citing papers in PubMed, 2 syntheses or guidelines pooled it, 179 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
- APOE ε4 and Dietary Patterns in Relation to Cognitive Function: An Umbrella Review of Systematic Reviews.Nutrition reviews · 2025Pooled it
- Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.Exploration (Beijing, China) · 2026Review
- Fibronectin mediates APOE4-driven blood-brain barrier dysfunction in Alzheimer's disease.Nature aging · 2026Article
- Review
- Relapse-associated worsening in apolipoprotein E ε4 carriers with relapsing multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Lower cardiac output is a risk factor for faster cerebral atrophy over a 11-year follow-up period in APOE-ε4 carriers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Article
- Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Friend or foe? Glial-vascular interactions in health and neurodegenerative disease.Pharmacological reviews · 2026Review
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Cell apoptosis in ischemic stroke: Focus on lipid metabolism.Neural regeneration research · 2026Article
- Integrated imaging and molecular profiling reveals APOE4-associated neurovascular and glial disruptions in young adult mice.Journal of neuroinflammation · 2026Article
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Molecular Mechanisms Underlying Alzheimer's Disease Pathogenesis: Comprehensive Overview.International journal of molecular sciences · 2026Review
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Three-dimensional interactive network: Mitochondrial-metabolic-calcium homeostasis driving Alzheimer's disease.Genes & diseases · 2026Review
74 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
7 authors at 1 institution in 1 country.
Funding
Abstract
Apolipoprotein E (ApoE) is a multifaceted secreted molecule synthesized in the CNS by astrocytes and microglia, and in the periphery largely by the liver. ApoE has been shown to impact the integrity of the blood-brain barrier, and, in humans, the APOE4 allele of the gene is reported to lead to a leaky blood-brain barrier. We used allele specific knock-in mice expressing each of the common (human) ApoE alleles, and longitudinal multiphoton intravital microscopy, to directly monitor the impact of various ApoE isoforms on blood-brain barrier integrity. We found that humanized APOE4, but not APOE2 or APOE3, mice show a leaky blood-brain barrier, increased MMP9, impaired tight junctions, and reduced astrocyte end-foot coverage of blood vessels. Removal of astrocyte-produced ApoE4 led to the amelioration of all phenotypes while the removal of astrocyte-produced ApoE3 had no effect on blood-brain barrier integrity. This work shows a cell specific gain of function effect of ApoE4 in the dysfunction of the BBB and implicates astrocyte production of ApoE4, possibly as a function of astrocytic end foot interactions with vessels, as a key regulator of the integrity of the blood-brain barrier.
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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.