Breakthrough in Alzheimer’s plaque treatment

Researchers at the University of Pennsylvania have successfully sent proteins across the blood-brain barrier to reduce the plaques associated with Alzheimer's disease.

The blood-brain barrier, which is a dense cluster of cells that only allows small molecules to pass through, plays a vital role in preventing infections from attacking the brain, but it also obstructs potential treatments for conditions such as Alzheimer's.

Led by professor Henry Daniell, the research team combined cholera toxin b (CTB), a receptor which targets neurons, with myelin basic protein (MBP), a molecule that breaks down the plaques believed to cause memory loss. The molecules were also able to cross the blood-retina barrier, enabling them to break down the plaques that form in the eyes of Alzheimer's sufferers.

In order to prove their initial hypothesis, the team fed a group of mice freeze-dried leaves which had been genetically engineered to express the fused proteins. A green-flourescent protein molecule was combined with the CTB carrier, allowing the team to ascertain whether the protein had reached the brain. The team were able to identify the molecule in the brains and the retinas of the mice.

"When we found the glowing protein in the brain and the retina we were quite thrilled," said Professor Daniell. "If the protein could cross the barrier in healthy mice, we thought it was likely that it could cross in Alzheimer's patients brains, because their barrier is somewhat impaired."

The research team exposed the brains of mice bred to have Alzheimer's disease to the CTB-MBP compound and administered a stain that binds to the brain plaques. Their results showed a reduction in staining, indicating that the plaques were dissolving. 

The same type of test was performed on brain tissue from patients who had died of Alzheimer's disease, resulting in a significant decrease in staining in the parietal cortex – a part of the brain associated with the development of the disease. 

Finally, capsules containing the CTB-MBP compound were given to mice that had been bred to develop Alzheimer's. A reduction in plaques was reported compared to a control group of mice that was fed a capsule containing lettuce leaves.

Professor Daniell hopes to expand his research to ascertain whether associated memory problems are reduced in mice after they ingest CTB-MBP.