NextFin news, On Monday, October 6, 2025, scientists from the Institute for Bioengineering of Catalonia (IBEC) and West China Hospital Sichuan University (WCHSU), in collaboration with partners in the UK and Spain, announced a breakthrough in Alzheimer's disease research. They successfully reversed Alzheimer's pathology in genetically engineered mice by using bioactive nanoparticles that restore the function of the blood-brain barrier (BBB), a critical vascular interface that protects the brain.
The study, published in the journal Signal Transduction and Targeted Therapy, introduces a novel therapeutic approach employing "supramolecular drugs"—nanoparticles that act as active agents rather than mere carriers of medication. These nanoparticles target and repair the BBB, which is often compromised in Alzheimer's disease, thereby enabling the brain to clear toxic waste proteins such as amyloid-β (Aβ) more effectively.
Alzheimer's disease is characterized by the accumulation of Aβ plaques in the brain, which impair neuronal function and lead to cognitive decline. The BBB normally regulates the brain's environment by controlling the passage of substances between the bloodstream and brain tissue. However, in Alzheimer's, this barrier's function deteriorates, hindering the clearance of harmful proteins.
The researchers used mouse models genetically predisposed to produce excessive Aβ and exhibit cognitive deficits similar to human Alzheimer's. After administering only three doses of the nanoparticles, they observed a rapid 50–60% reduction in brain Aβ levels within one hour. Behavioral tests conducted over several months showed that treated mice regained memory and cognitive abilities comparable to healthy controls, even when treatment began at advanced disease stages.
Giuseppe Battaglia, ICREA Research Professor at IBEC and lead investigator, explained that the nanoparticles act by mimicking ligands of the LRP1 receptor, a molecular gatekeeper responsible for transporting Aβ across the BBB into the bloodstream for elimination. By modulating LRP1 function, the nanoparticles restore the natural clearance pathway, allowing the brain's vascular system to recover and maintain homeostasis.
Junyang Chen, first co-author and researcher at West China Hospital and University College London, highlighted the speed and efficacy of the treatment, noting the significant reduction in Aβ shortly after injection. Lorena Ruiz Perez, co-author and Serra Hunter Assistant Professor at the University of Barcelona, emphasized the therapeutic potential of this vascular-targeted strategy for Alzheimer's disease.
This research underscores the importance of vascular health in neurodegenerative diseases and offers a promising new direction for clinical interventions aimed at restoring BBB function and enhancing brain waste clearance. The study was a collaborative effort involving IBEC, WCHSU, University College London, University of Barcelona, Chinese Academy of Medical Sciences, and other institutions.
The full study is available in Signal Transduction and Targeted Therapy (2025), DOI: 10.1038/s41392-025-02426-1.
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