Alzheimer's disease reversed in mice using nanoparticles

By using bioactive particles to repair the blood-brain barrier, which acts as a barrier against toxins and pathogens, scientists restored vascular balance in the brain and reversed the disease in animal models. The study was led by the Institute of Bioengineering of Catalonia and West China Hospital.

An international team co-led by the Institute for Bioengineering of Catalonia (IBEC) and the West China Hospital of Sichuan University (WCHSU), with the participation of researchers from the United Kingdom, has demonstrated a nanotechnology strategy that reverses Alzheimer's disease in mice.

Unlike conventional nanomedicine, which uses nanoparticles As drug carriers, this method uses bioactive particles themselves, called supramolecular drugs. Instead of targeting neurons, the treatment acts on the blood brain barrier (BBB), the interface that regulates the brain's environment. By repairing this barrier, which acts as a guard against toxins and pathogens, scientists were able to restore the balance of the cerebral vascular system and reverse the pathology in animal models.

The brain consumes 20% of its energy in adults and up to 60% in children, through a dense network of capillaries. When the blood-brain barrier is compromised, the brain cleaning system stops working properly, which promotes the accumulation of the amyloid beta protein (Aβ), one of the main characteristics of Alzheimer's.

Direct to the bloodstream

The researchers managed to get the nanoparticles to allow these waste proteins to pass into the bloodstream for elimination. In mouse models genetically programmed to produce large amounts of Aβ and develop cognitive decline, administering just three doses achieved remarkable results.

“Just one hour after the injection, we observed a 50-60% reduction in the amount of Aβ in the brain,” he explains. Junyang Chen, co-first author of the study and a researcher at West China Hospital and University College London.

Beyond the immediate elimination of toxic proteins, the team observed therapeutic effects durable. In one experiment, a 12-month-old mouse (equivalent to a 60-year-old human) received the treatment and was analyzed six months later. At 18 months, an age comparable to 90 years in humans, the animal displayed behavior similar to that of a healthy mouse.

“The long-term effect comes from the restoration of the brain's vascular system"We believe it works like a cascade: when the vascular system recovers its function, it begins to eliminate Aβ and other harmful molecules, allowing the system to rebalance. Our nanoparticles act like a drug and appear to activate a feedback mechanism that normalizes this elimination pathway," he says. Joseph Battaglia, ICREA research professor at IBEC and leader of the study.

Supramolecular drugs

Under normal conditions, the LRP1 protein transports amyloid beta across the blood-brain barrier for removal. This process can be blocked if the protein binds excessively, or insufficient if the signal is too weak, both facilitating accumulation in the brain.

The developed supramolecular drugs mimic LRP1 ligands, promoting Aβ transport and restoring the natural cleansing system. Thus, they help restore vascular balance and brain function.

“We demonstrated significant efficacy in achieving rapid clearance of Aβ, restoring blood-brain barrier function, and reversing Alzheimer’s disease,” he concludes. Lorena Ruiz Pérez, researcher in the Molecular Bionics group at IBEC and Serra Hunter assistant professor at the University of Barcelona.

Molecular engineering 

The work introduces a molecular engineering strategy that designs nanoparticles with precise size control and surface ligands capable of interacting specifically with cellular receptors. According to the authors, this method could pave the way for new clinical interventions targeting the vascular mechanisms of Alzheimer's.

The study was the result of the collaboration between IBEC, West China Hospital and Xiamen West China Hospital of Sichuan University, University College London, the University of Barcelona, ​​the Chinese Academy of Medical Sciences and the Catalan Institution for Research and Advanced Studies (ICREA).

Source: SINC Agency