Nanoparticles reduce Alzheimer’s plaques in mouse study

Biodegradable nanoparticles already widely used to deliver medicines could have therapeutic effects of their own in Alzheimer’s disease. Researchers at the University of Alberta found that polylactic-co-glycolic acid (PLGA) nanoparticles reduced molecular and cellular signs of the disease and improved cognitive and memory functions in mice.

The findings are preclinical. Further research will be needed to establish whether the effects can be reproduced and eventually translated into a treatment for people with Alzheimer’s disease.

Nanoparticles without added drugs

PLGA nanoparticles have a long history in medicine. Initially used in biodegradable sutures, they were subsequently approved as drug-delivery vehicles. More than 20 medicines are now delivered using PLGA nanoparticles, which can be modified to target specific organs or tissues.

Satyabrata Kar, professor in the University of Alberta’s Department of Medicine, has studied their potential in Alzheimer’s disease since 2020. Previous research by his team indicated that the nanoparticles can protect neurons against toxicity and inhibit the aggregation of neuronal proteins associated with the disease.

In the latest study, however, PLGA nanoparticles were investigated without an additional therapeutic drug. When delivered directly into the brains of mice with Alzheimer’s disease, the particles prevented the overproduction and accumulation of beta-amyloid peptides. These peptides can aggregate into the plaques characteristic of Alzheimer’s disease. The researchers also observed improvements in cognitive and memory functions following treatment.

Multiple effects

Exactly why PLGA nanoparticles produced these effects remains unclear. According to Kar, the particles appear to influence several factors involved in the disease process. He also reports that another laboratory in the United States has reproduced some of his team’s findings.

Despite the encouraging results, significant questions remain before the approach could be considered for human use. The current experiments involved direct delivery to the brains of animals, while a clinically practical treatment would need to address how the nanoparticles reach their target effectively and safely. Kar is collaborating with other researchers to investigate how PLGA nanoparticles cross the blood-brain barrier and how their half-life could be extended so that they remain active for longer.

Potential role in diagnosis

The researchers are also exploring applications beyond treatment. A separate collaboration is investigating whether labelled PLGA nanoparticles can bind to plaques in the brain. If successful, this could potentially support faster detection of Alzheimer’s-related pathology.

PLGA already has an established safety record as a biodegradable material and drug-delivery vehicle, but that does not establish the safety or effectiveness of this experimental Alzheimer’s approach. Kar plans further studies to validate the findings and better understand the mechanisms involved.

The research therefore remains at an early stage. The mouse results suggest an unexpected therapeutic potential for a material already familiar to medicine, but further preclinical research will be essential before its relevance to patients can be determined.

Monitoring plaques

Last year, an international research team developed a fibre optic method to monitor amyloid plaque accumulation in the brains of living, freely moving mice. The technique adapts fibre photometry using Methoxy-X04, a fluorescent dye that crosses the blood-brain barrier and binds to amyloid fibrils. Tests in Alzheimer’s mouse models showed that fluorescence signals correlated strongly with plaque density. Tapered optical fibres also enabled measurements at different brain depths, detecting disease-related increases in fluorescence that were absent in healthy controls.

Unlike techniques that require anaesthesia, the method can monitor awake animals over longer periods and in deeper brain structures. Although it cannot yet distinguish individual plaques, the researchers believe it could support preclinical Alzheimer’s research by tracking disease progression and helping evaluate whether experimental treatments slow amyloid accumulation.