ArticleInternational journal of molecular sciences2021
Blood-Brain Barrier Disruption Increases Amyloid-Related Pathology in TgSwDI Mice.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Emerging diagnostic biomarkers and therapeutic targets in Alzheimer's disease.Inflammopharmacology · 2026Review
- Convergence of neuroinflammation across major neurotropic viral exposomes in AD and ADRD.Journal of neuroinflammation · 2026Review
- Effect of high altitude on the pharmacokinetics and pharmacodynamics of valproate in epileptic rats.Frontiers in pharmacology · 2026Article
- Chronic Treatment of a Mouse Model of Cerebral Amyloid Angiopathy and Brain ATbioRxiv : the preprint server for biology · 2025Article
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- Reduction of orexin-expressing neurons and a unique sleep phenotype in the Tg-SwDI mouse model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- 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
- Blood-Brain Barrier Breakdown in Alzheimer's Disease: Mechanisms and Targeted Strategies.International journal of molecular sciences · 2023Review
- Blood-brain barrier breakdown is linked to tau pathology and neuronal injury in a differential manner according to amyloid deposition.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- The Blood-Brain Barrier in Health and Disease.International journal of molecular sciences · 2023Article
- Lenvatinib resistance mechanism and potential ways to conquer.Frontiers in pharmacology · 2023Review
- Cooperation between neurovascular dysfunction and Aβ in Alzheimer's disease.Frontiers in molecular neuroscience · 2023Review
- Discerning the Role of Blood Brain Barrier Dysfunction in Alzheimer's Disease.Aging and disease · 2022Article
- A curated binary pattern multitarget dataset of focused ATP-binding cassette transporter inhibitors.Scientific data · 2022Article
- Transporter Regulation in Critical Protective Barriers: Focus on Brain and Placenta.Pharmaceutics · 2022Review
- The "Cerebrospinal Fluid Sink Therapeutic Strategy" in Alzheimer's Disease-From Theory to Design of Applied Systems.Biomedicines · 2022Review
- Perphenazine and prochlorperazine decrease glioblastoma U-87 MG cell migration and invasion: Analysis of the ABCB1 and ABCG2 transporters, E-cadherin, α-tubulin and integrins (α3, α5, and β1) levels.Oncology letters · 2022Article
- Relationship Between Amyloid-β Deposition and Blood-Brain Barrier Dysfunction in Alzheimer's Disease.Frontiers in cellular neuroscience · 2021Review
- Binding mode analysis of ABCA7 for the prediction of novel Alzheimer's disease therapeutics.Computational and structural biotechnology journal · 2021Article
- Tracking pericyte dysfunction in Alzheimer's disease: The emerging role of cerebrospinal fluid platelet-derived growth factor receptor-β.Tzu chi medical journalReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In Alzheimer's disease (AD), several studies have reported blood-brain barrier (BBB) breakdown with compromised function. P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are transport proteins localized at the BBB luminal membrane and play an important role in the clearance of amyloid-β (Aβ). The purpose of this study was to investigate the effect of pharmacological inhibition of Aβ efflux transporters on BBB function and Aβ accumulation and related pathology. Recently, we have developed an in vitro high-throughput screening assay to screen for compounds that modulate the integrity of a cell-based BBB model, which identified elacridar as a disruptor of the monolayer integrity. Elacridar, an investigational compound known for its P-gp and BCRP inhibitory effect and widely used in cancer research. Therefore, it was used as a model compound for further evaluation in a mouse model of AD, namely TgSwDI. TgSwDI mouse is also used as a model for cerebral amyloid angiopathy (CAA). Results showed that P-gp and BCRP inhibition by elacridar disrupted the BBB integrity as measured by increased IgG extravasation and reduced expression of tight junction proteins, increased amyloid deposition due to P-gp, and BCRP downregulation and receptor for advanced glycation end products (RAGE) upregulation, increased CAA and astrogliosis. Further studies revealed the effect was mediated by activation of NF-κB pathway. In conclusion, results suggest that BBB disruption by inhibiting P-gp and BCRP exacerbates AD pathology in a mouse model of AD, and indicate that therapeutic drugs that inhibit P-gp and BCRP could increase the risk for AD.
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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.