Amyloid Proteins Are Target for New Alzheimer’s Vaccine

Georgia Health Sciences University graduate student Scott Webster says that targeting the amyloid protein and its pathways could lead to the development of a new type of vaccine against Alzheimer's.

The disease, a neurodegenerative form of dementia, is incurable and fatal over time. It first acts by reducing patients' higher cognitive functions, starting with their memory. Prevention is the only way to keep the condition in check, but not many people go through the necessary paces.

One of the most important actors in Alzheimer's is the amyloid protein, which has the nasty habit of accumulating in the brain in far larger quantities than baseline levels. As it does so, it lodges itself amid nerve cells, forming blockages called amyloid plaques.

When the body is functioning normally, excess amounts of the protein are eliminated by the body's natural defenses, but that process somehow fails in Alzheimer's disease. According to Webster, scientists could contribute to this mechanism with a new vaccine.

In addition to the protein itself, the team also discovered that another class of proteins – called receptor for advanced glycation endproducts (RAGE) – also play an important role in the development of Alzheimer's. They tend to bind to amyloid and carry the latter in the brain, where it accumulates.

Recent investigations have also demonstrated that the RAGE molecules may also be responsible for augmenting amyloid's ability to cause inflammation and other types of damages in the human brain, Science Blog reports.

Working in the lab of GHSU professor of pharmacology and toxicology Dr. Alvin Terry, Webster was able to research a vaccine that works by boosting the body's own natural defenses in the fight against the combined forces of RAGE and amyloid proteins.

What the immune system needs to prevent is the over-production of the two molecules, as this is the primary factor that leads to their build-up between neurons. For his work, Webster won the 2011 Darrell W. Brann Scholarship in Neuroscience.

“Unfortunately, all of the vaccines for Alzheimer’s that have been through clinical trials have failed. Part of the reason why could be that they’re just not comprehensive enough,” the student explains.

“Most only target amyloid. Our hope is that by taking a more encompassing approach, we will be more effective. So far, that’s exactly what we’re seeing in our experiments,” Webster goes on to say.

“That’s a relatively new idea. By using the immune system that’s endogenous to our gut, we can skew the body’s response away from the inflammatory and toward a more robust antibody response, bypassing some of the side effects,” he concludes.