ArticleSignal transduction and targeted therapy2025
Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood-brain barrier transport.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The trial behind it
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Who cites it
27 citing papers in PubMed.
- Increased Amyloidogenic Neuronal Injury in HIV-1-infected APP-KI Alzheimer's disease mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Female vulnerability to microvascular transport dysfunction emerges early across the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A collaborative framework for uncovering molecular and cellular drivers of VCID: Foundations for future interventions in dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- A computational analysis of the glycoprotein lipoprotein receptor-related protein 1 structure and the role of glycans as quaternary glue.Bioinformatics (Oxford, England) · 2026Article
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Avidity-by-design: spatial control of T7 peptide presentation on polymersomes dictates blood-brain barrier transport fate.Drug delivery and translational research · 2026Article
- Transport pathways across the blood-brain barrier for waste clearance and drug delivery.Fluids and barriers of the CNS · 2026Review
- NIR-II Imaging-Guided Photothermal Activation of a TRPV4-Targeted Nanoplatform Delivering Cycloastragenol to Promote Microglia Reprogramming and α-Synuclein Clearance in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advances in Strategies to Transport Nanoparticles Across the Blood-Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A Review of the Effect of Peripheral Amyloid β on the Central Nervous System.Current issues in molecular biology · 2026Review
- Recent advances in lipid and biomimetic nanocarriers for nucleic acid delivery in glioblastoma.Discover oncology · 2026Review
- Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses microglial inflammation in Alzheimer's disease models.Scientific reports · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Research progress of blood-brain barrier penetrating and brain diseases therapy by natural biopolymer - based nanomedicine delivery systems.Materials today. Bio · 2026Review
- Anti-Inflammatory and Antioxidant Effects of ω-3 Polyunsaturated Fatty Acids on Astrocytes and Their Implications for the Blood-Brain Barrier's Integrity and Function.International journal of molecular sciences · 2026Review
- New Strategies for the Prevention and Therapy of Alzheimer's Disease Based on Stimulation of Brain Drainage and Lymphatic Clearance.International journal of molecular sciences · 2026Review
- Review
- CD147/Basigin: From Integrative Molecular Hub to Translational Therapeutic Target.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- FDA-Approved Passive Immunization Treatments Against Aβ in Alzheimer's Disease: Where Are We Now?International journal of molecular sciences · 2026Review
- APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells.Frontiers in molecular biosciences · 2026Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
The blood‒brain barrier (BBB) is a highly selective permeability barrier that safeguards the central nervous system (CNS) from potentially harmful substances while regulating the transport of essential molecules. Its dysfunction is increasingly recognized as a pivotal factor in the pathogenesis of Alzheimer's disease (AD), contributing to the accumulation of amyloid-β (Aβ) plaques. We present a novel therapeutic strategy that targets low-density lipoprotein receptor-related protein 1 (LRP1) on the BBB. Our design leverages the multivalent nature and precise size of LRP1-targeted polymersomes to modulate receptor-mediated transport, biasing LRP1 trafficking toward transcytosis and thereby upregulating its expression to promote efficient Aβ removal. In AD model mice, this intervention significantly reduced brain Aβ levels by nearly 45% and increased plasma Aβ levels by 8-fold within 2 h, as measured by ELISA. Multiple imaging techniques confirmed the reduction in brain Aβ signals after treatment. Cognitive assessments revealed that treated AD mice exhibited significant improvements in spatial learning and memory, with performance levels comparable to those of wild-type mice. These cognitive benefits persisted for up to 6 months post-treatment. This work pioneers a new paradigm in drug design, where function arises from the supramolecular nature of the nanomedicine, harnessing multivalency to elicit biological action at the membrane trafficking level. Our findings also reaffirm the critical role of the BBB in AD pathogenesis and demonstrate that targeting the BBB can make therapeutic interventions significantly more effective. We establish a compelling case for BBB modulation and LRP1-mediated Aβ clearance as a transformative foundation for future AD therapies.
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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.