ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood-brain barrier function in mice.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 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
- Preclinical in-vivo cerebrovascular imaging in rodent models: Methods and applications in Alzheimer's disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Review
- Connecting the Dots: Neurobiological Interplay Between Type 2 Diabetes and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Is there a role for apolipoprotein E in perinatal brain injury?Molecular and cellular pediatrics · 2026Review
- APOE-ε4 genotype and western diet synergistically aggravate synaptic dysfunction in Alzheimer's disease via D-serine disruption.Alzheimer's research & therapy · 2026Article
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- Counteracting white matter injury to mitigate APOE 𝜀4-related ARIA.Alzheimer's & dementia : the journal of the Alzheimer's Association · 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
- Memory deficits in hypertensive ApoE4 mice reversed by P2Y12 inhibition via different mechanisms in males and perimenopausal females.Research square · 2025Article
- The Therapeutic Potential of Glymphatic System Activity to Reduce the Pathogenic Accumulation of Cytotoxic Proteins in Alzheimer's Disease.International journal of molecular sciences · 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
- Exercise-mediated cerebrovascular repair in Alzheimer's disease: from pathophysiology to therapeutic precision.Frontiers in aging neuroscience · 2025Review
- APOE 𝜀4-related blood-brain barrier breakdown is associated with microstructural abnormalities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Is the Relationship Between Cardiovascular Disease and Alzheimer's Disease Genetic? A Scoping Review.Genes · 2024Article
- A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury.Nature neuroscience · 2024Article
- Microvascular and cellular dysfunctions in Alzheimer's disease: an integrative analysis perspective.Scientific reports · 2024Article
- Cerebral microvascular changes in healthy carriers of the APOE-ɛ4 Alzheimer's disease risk gene.PNAS nexus · 2024Article
- Lower GLUT1 and unchanged MCT1 in Alzheimer's disease cerebrovasculature.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
50 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood-brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [(3)H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [(3)H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development.
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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 OpenQuestion graph.