ArticleScience advances2015
Autoregulated paracellular clearance of amyloid-β across the blood-brain barrier.
Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed, 149 citations in OpenAlex.
- Theranostic Innovative Strategies for Brain Diseases: New Insights on Neurovascular Unit-Associated Pathological Changes in Neurodegenerative Disorders and Aging.International journal of molecular sciences · 2026Review
- Vascular Endothelial Barrier in Salivary Glands: From Physiological Regulation to Pathological Impairment of Secretion.International journal of molecular sciences · 2026Review
- Functional Pathological Features and Molecular Markers in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Living arrangements and cognitive resilience in aging: unraveling distinct pathways through plasma biomarkers.The journal of prevention of Alzheimer's disease · 2026Article
- Trauma exposure, PTSD, and methylation of the blood brain barrier claudin-5 gene.Psychoneuroendocrinology · 2026Article
- Investigation of Serum Claudin-5 Levels in Patients with Heroin Addiction.Medeniyet medical journal · 2026Article
- Article
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- Increased neurotoxic gliosis and blood-brain barrier dysregulation in canine cognitive dysfunction syndrome (CCD).Frontiers in aging · 2026Article
- Influence of Alzheimer's associated Aβ oligomers and oxidative stress on blood-brain barrier dysfunction.Tissue barriers · 2026Article
- The Breakdown of Neurovascular Barriers: Molecular Mechanisms of Tight Junction Dysfunction.Molecular neurobiology · 2025Review
- Trauma Exposure, PTSD, and Methylation of the Blood Brain Barrier Claudin-5 Gene.medRxiv : the preprint server for health sciences · 2025Article
- Cholesterol Depletion with U18666A and Methyl-β Cyclodextrin Increased Small Molecule Permeability Across Brain Microvascular Endothelial Cells.Annals of biomedical engineering · 2025Article
- Endothelial-to-mesenchymal transition in the central nervous system: A potential therapeutic target to combat age-related vascular fragility.The Journal of pharmacology and experimental therapeutics · 2025Review
- Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.Alzheimer's research & therapy · 2025Article
- Assessing blood-brain barrier (BBB) integrity in an Alzheimer's disease mouse model: is the BBB globally or locally disrupted?Fluids and barriers of the CNS · 2025Article
- 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
- Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications.Antioxidants (Basel, Switzerland) · 2025Review
- How is the brain affected by metabolically healthy or unhealthy obesity in adulthood and elderly? A narrative review of neuroimaging and neurocognitive findings.Frontiers in aging neuroscience · 2025Review
- LRP1 at the crossroads of Aβ clearance and therapeutic targeting in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
30 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
14 authors at 4 institutions in 3 countries.
Funding
Abstract
The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and protecting neural tissue from damaging blood-borne agents. The barrier is characterized by endothelial tight junctions that limit passive paracellular diffusion of polar solutes and macromolecules from blood to brain. Decreased brain clearance of the neurotoxic amyloid-β (Aβ) peptide is a central event in the pathogenesis of Alzheimer's disease (AD). Whereas transport of Aβ across the BBB can occur via transcellular endothelial receptors, the paracellular movement of Aβ has not been described. We show that soluble human Aβ(1-40) monomers can diffuse across the paracellular pathway of the BBB in tandem with a decrease in the tight junction proteins claudin-5 and occludin in the cerebral vascular endothelium. In a murine model of AD (Tg2576), plasma Aβ(1-40) levels were significantly increased, brain Aβ(1-40) levels were decreased, and cognitive function was enhanced when both claudin-5 and occludin were suppressed. Furthermore, Aβ can cause a transient down-regulation of claudin-5 and occludin, allowing for its own paracellular clearance across the BBB. Our results show, for the first time, the involvement of the paracellular pathway in autoregulated Aβ movement across the BBB and identify both claudin-5 and occludin as potential therapeutic targets for AD. These findings also indicate that controlled modulation of tight junction components at the BBB can enhance the clearance of Aβ from the brain.
Identifiers
What OpenQuestion holds
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.