A new Alzheimer’s treatment in mice worked fast, and the researchers say it did it by getting the brain’s own cleanup system working again.

An international team led by the Institute for Bioengineering of Catalonia and West China Hospital Sichuan University reported that specially engineered nanoparticles reduced toxic amyloid-β buildup, repaired the blood-brain barrier and reversed Alzheimer’s-like symptoms in mice. The findings were published in Signal Transduction and Targeted Therapy.

Instead of targeting damaged neurons directly, the scientists focused on the blood-brain barrier, a network of cells and blood vessels that controls what enters and leaves the brain. In Alzheimer’s disease, the researchers said this system breaks down, allowing harmful proteins to accumulate and brain function to worsen over time.

The team designed bioactive nanoparticles, described as supramolecular drugs, to restore the barrier and restart the brain’s ability to remove waste.

The researchers tested the therapy in genetically engineered mice that develop high levels of amyloid-β and progressive cognitive decline similar to Alzheimer’s disease in humans. The animals received three doses of the nanoparticles.

“Only 1h after the injection we observed a reduction of 50-60% in Aβ amount inside the brain,” said Junyang Chen, first co-author of the study, a researcher at the West China Hospital of Sichuan University and a PhD student at University College London.

Scientists then tracked the mice for months using behavioural and memory tests at different stages of disease progression.

In one experiment, the researchers treated a 12-month-old mouse, described as equivalent to a 60-year-old human, and tested it again six months later. By then, the mouse was described as roughly comparable to a 90-year-old human, but it behaved similarly to a healthy animal with no signs of Alzheimer’s-related decline.

“The long-term effect comes from restoring the brain’s vasculature. We think it works like a cascade: when toxic species such as amyloid-beta (Aβ) accumulate, disease progresses. But once the vasculature is able to function again, it starts clearing Aβ and other harmful molecules, allowing the whole system to recover its balance. What’s remarkable is that our nanoparticles act as a drug and seem to activate a feedback mechanism that brings this clearance pathway back to normal levels,” said Giuseppe Battaglia, ICREA research professor at IBEC, principal investigator of the Molecular Bionics Group and leader of the study.

A major focus of the study was LRP1, a protein at the blood-brain barrier that binds amyloid-β and moves it out of the brain and into the bloodstream for disposal. The researchers said the nanoparticles were engineered to mimic the natural molecules that interact with LRP1, appearing to reset the transport system so amyloid-β could move out of the brain again.

The team said the approach differs from many traditional Alzheimer’s therapies because the nanoparticles are the treatment themselves, rather than carriers used to deliver another drug. They were built using a molecular engineering process that allowed the researchers to control their size and the number of ligands on their surface.

The researchers said that precision helped the particles interact with receptors on cell membranes in specific ways, improving amyloid-β clearance and restoring healthier blood vessel activity in the brain.

The work is still at the animal-testing stage. The project involved researchers from IBEC, West China Hospital of Sichuan University, West China Xiamen Hospital of Sichuan University, University College London, the Xiamen Key Laboratory of Psychoradiology and Neuromodulation, the University of Barcelona, the Chinese Academy of Medical Sciences and ICREA.

“Our study demonstrated remarkable efficacy in achieving rapid Aβ clearance, restoring healthy function in the blood-brain barrier and leading to a striking reversal of Alzheimer’s pathology,” said Lorena Ruiz Perez, a researcher at the Molecular Bionics Group at IBEC and Serra Hunter assistant professor at the University of Barcelona.

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