ArticleFluids and barriers of the CNS2025
Transferrin receptor-binding blood-brain barrier shuttle enhances brain delivery and plaque-clearing efficacy of a therapeutic anti-Aβ antibody.
Article in Fluids and barriers of the CNS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Therapeutic role of GLP-1 receptor agonists in idiopathic intracranial hypertension: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- PLXDC2 siRNA-Mediated Intervention Attenuates Microglial Senescence Through cGAS-STING Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Development of a Human IgG1 Monoclonal Antibody Targeting Transferrin Receptor 1 for Antitumor Drug Delivery.Antibodies (Basel, Switzerland) · 2026Article
- Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification.Drug design, development and therapy · 2026Review
- Anti-Aβ3-10 monoclonal antibody 7B8 improves cognitive function and protects the blood-brain barrier in APP/PS1 mice by regulating the HMGB-1/RAGE/NF-κB pathway.Frontiers in immunology · 2026Article
- Targeting microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and therapeutic approaches.Frontiers in immunology · 2026Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTransferrin receptor-1 (TfR1) transcytosis-mediated delivery of therapeutic monoclonal antibodies across the blood-brain barrier (BBB) is a promising concept in drug development for CNS disorders. In this study, we investigated brain delivery and effects on plaque burden of Aducanumab (Adu), a clinically validated anti-amyloid beta (Aβ) antibody, when fused to a mouse TfR1-binding Fab fragment as BBB shuttle (TfR1-Adu).
methodsWhole-organ clearing and immunolabeling coupled with light sheet fluorescence microscopy of whole brain hemispheres was applied for quantitative 3D assessment of brain distribution of therapeutic antibodies and plaque burden in a transgenic APP/PS1 mouse model of Alzheimer's disease (AD).
resultsCompared to unmodified Adu, TfR1-Adu demonstrated enhanced brain delivery and a more homogeneous brain distribution following both acute and chronic systemic administration. Additionally, the addition of the TfR1 shuttle mitigated the periarterial drug distribution observed with unmodified Adu. While high-dose chronic Adu was able to reduce Aβ plaque burden across multiple brain regions, a comparable reduction in plaque burden was achieved with a five-fold lower dose of TfR1-Adu.
conclusionsCollectively, these findings provide strong support for the use of TfR1-mediated BBB shuttle strategies to enhance brain delivery of anti-Aβ antibodies and thereby reduce amyloid plaque burden, while highlighting the value of advanced whole-brain imaging platforms to guide the rational development of next-generation drugs for AD and other CNS disorders.
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