In a groundbreaking study, scientists from the Institute for Bioengineering of Catalonia (IBEC) and West China Hospital Sichuan University (WCHSU) have developed a nanoparticle-based therapy that reverses Alzheimer’s disease in mice. Unlike traditional nanomedicine, which uses nanoparticles as passive carriers, this new approach employs “supramolecular drugs”. These are nanoparticles that are therapeutically active themselves. The study, published in Signal Transduction and Targeted Therapy, marks a major step forward in Alzheimer’s research and vascular-based brain therapies.
Restoring the brain’s natural defense system
Instead of targeting neurons directly, the therapy focuses on restoring the blood–brain barrier (BBB), the brain’s natural filtration system that controls the exchange of substances between blood and neural tissue. When this barrier is damaged, harmful proteins like amyloid-beta (Aβ) can accumulate, leading to neurodegeneration.
Using mouse models genetically engineered to develop Alzheimer’s-like pathology, researchers administered just three doses of the supramolecular drugs. Within one hour, they observed a 50–60% reduction in Aβ accumulation in the brain. Even more striking, after six months, the treated mice, equivalent in age to 90-year-old humans, regained normal cognitive behavior.
“The long-term recovery stems from restoring vascular function. Once the vasculature can clear amyloid-beta again, the brain begins to heal itself, regaining balance and function”, explains Prof. Giuseppe Battaglia, ICREA Research Professor at IBEC.
How supramolecular nanoparticles work
In Alzheimer’s disease, the LRP1 protein normally helps transport amyloid-beta out of the brain. But this system breaks down when LRP1 becomes overloaded or degraded, causing toxic buildup. The supramolecular nanoparticles developed by the team act as molecular reset switches, mimicking natural LRP1 ligands to bind Aβ and ferry it safely through the BBB into the bloodstream for elimination.
This strategy not only clears amyloid-beta but also restores vascular health, reactivating the brain’s ability to remove waste products and regulate its internal environment. Designed using molecular-level engineering, these nanoparticles are fine-tuned for size, shape, and surface chemistry. Their precise multivalent design allows them to interact specifically with cellular receptors, enabling a highly controlled modulation of brain signaling, a level of precision that conventional drugs cannot achieve.
A new therapeutic frontier for neurodegenerative disease
“Our findings show that nanomedicine can go beyond delivery. The nanoparticles themselves can act as active drugs,” says Dr. Lorena Ruiz Perez of IBEC and the University of Barcelona. “By restoring blood–brain barrier function and clearing amyloid-beta efficiently, we were able to reverse Alzheimer’s pathology in our models.”
This breakthrough highlights the crucial role of vascular health in brain diseases and suggests a new therapeutic direction for conditions like Alzheimer’s, dementia, and other neurovascular disorders. By focusing on the blood–brain interface, rather than neurons alone, the study opens possibilities for safer, more effective treatments that restore the brain’s natural resilience.
The research, a collaboration among IBEC, WCHSU, University College London, and the University of Barcelona, demonstrates that targeting the brain’s vascular system could hold the key to combating one of medicine’s most challenging diseases. “Our nanoparticles don’t just treat symptoms. They help the brain repair itself. This could be the foundation for the next generation of Alzheimer’s therapies”, concludfes Prof. Battaglia. The study was recently published in Nature Communications.
Digital platform
Last year, Belgian researchers from six universities and university hospitals launched Translate-AD, a three-year research project to create a secure digital platform for sharing Alzheimer’s patient data and expertise. The initiative aims to accelerate collaboration, improve early diagnosis, and support more effective treatments.
Alzheimer’s is the leading cause of death in Belgium, but research progress has been hindered by strict privacy laws limiting data exchange. Translate-AD addresses this by allowing analyses to be performed locally on hospital servers, where anonymized data remains securely stored. Only aggregated results are shared, ensuring compliance with privacy regulations.
The platform will also centralize biomarker information to identify which patients benefit most from emerging therapies. AI-based security safeguards patient data, while regular meetings keep participants informed. This innovative approach builds on the Personal Health Train model, bringing research to the data rather than moving data across systems.
