Nanoparticle Injection Reverses Cognitive Decline in Mice With Alzheimer's Model

A single injection of a nanoparticle treatment designed to trigger the growth of new brain cells reversed cognitive decline in mice bred to model Alzheimer's disease, according to US researchers. The treatment could one day help restore the brain's ability to recover from ongoing nerve-cell loss in patients with advanced dementia, though its use in humans is still some way off.

Alzheimer's disease involves a steady loss of neurons to inflammation that the brain cannot quickly replace in areas such as the hippocampus, a brain region involved in memory, leading to lost memory and cognition. Most approved treatments target inflammation to slow this loss, but none can replace brain cells faster than they disappear.

The team, led by senior author Peisheng Xu, a pharmaceutical researcher at the University of South Carolina, targeted astrocytes, star-shaped support cells that can transform into neurons under the right conditions. A protein called PTBP1 normally blocks this transformation, so the researchers built a nanogel-based delivery system, called Nano-ERASER, to carry PTBP1-targeting antibodies across the blood-brain barrier, a protective layer that normally keeps most substances out of the brain, and suppress the protein's activity.

Within weeks of an injection, mice with signs of neurodegeneration built better nests and navigated mazes more successfully, both signs of improved memory, and their brains showed higher neuron density than untreated mice. "The new neurons can become mature and survive," said Xu. "After just two injections, these mice became smarter." The findings were published in the journal Cell Biomaterials.