New Vaccine Takes Down Toxic Plaques Associated with Alzheimer's

Alzheimer's disease — an irreversible, progressive brain disorder — is the sixth leading cause of death in the US and more than afflicts 5 million Americans. As if those numbers aren't scary enough, the Centers for Disease Control and Prevention expect that number to nearly triple by 2050.

What causes the disease and how to stop or prevent it are topics of intense scientific investigation. Central to those efforts is the study of amyloid plaques — clumps of sticky proteins pieces in the brain — a hallmark of the disease.

In an attempt to prevent amyloid plaque accumulation, two recent studies from the Peter O'Donnell Jr. Brain Institute report promising results in animals with a new DNA vaccine.

The studies appeared in the in the April online version of Alzheimer's Research & Therapy and in March issue of the Journal of Alzheimer's Disease.

Amyloid Deposits — Cause or Effect?

Amyloid deposits sit squarely in the middle of a controversy surrounding their role in Alzheimer's disease. Scientists debate whether they cause the disease or are a product of it.

What we know is that amyloid plaques accumulate in the brain as Alzheimer's progresses. But amyloid proteins are present in all our cells. In neurons of the brain — for reasons unknown — they can be cut by enzymes, creating sticky snippets that clump together into plaques. The deposits of plaques start a cascade that involves the formation of neurofibrillary tangles with a protein called tau. These changes lead to loss of connections between brain neurons, their eventual death, and the symptoms of Alzheimer's — loss of memory and thinking skills, and progressive dementia.

The DNA Vaccine Difference

Scientists have already developed vaccines to prevent or remove plaques. Immunization against amyloid protein removed plaques and improved memory tests in mice with Alzheimer's disease, but trials of the vaccine in humans had to be stopped because some people developed encephalitis, swelling of the brain.

Clinical trials using antibodies created in the lab against parts of the amyloid protein are underway. These preformed antibodies don't activate the body's immune response, so the hope is that they will not cause encephalitis as the vaccines did. However, they only respond to small parts of the amyloid protein.

Roger Rosenberg, MD, co-author of both studies and Director of the Alzheimer's Disease Center at UT Southwestern Medical Center, decided to approach his team's vaccine development from a different angle.

He chose to use an active immunization approach, which, instead of directly injecting already created antibodies, would allow the body to produce its own antibodies against the plaques. First, they had to develop a technique to do it safely. Vaccines are more accessible and less expensive than injections of antibody produced in the lab, and vaccination produces a wider variety of antibody types.

All the vaccines we received as kids and adults have been active vaccinations; we made the antibodies in the body. It's safer, more effective, and it's sustained longer.

— Rosenberg via press release

Rosenberg's idea was to start with DNA that codes for amyloid protein production and to inject it into the skin, rather than the muscle used for the failed human vaccine study. Once injected into the skin cells, the DNA would be used to produce amyloid protein, and the body would respond by producing antibodies to it and prevent the build-up that causes Alzheimer's.

The two recently published studies showed that the DNA vaccine was safe and effective in rabbits and monkeys. The vaccine activated an immune response that produced more than 40 times more anti-amyloid antibody than a vaccine Rosenberg tested years earlier.

New Vaccine Takes Down Toxic Plaques Associated with Alzheimer's — Amyloid plaque in the mouse brain detected with fluorescent anti-amyloid antibody (left) from large mammals immunized with the DNA vaccine. *Image via UT Southwestern*

But will producing antibodies to amyloid protein be enough to stop Alzheimer's?

"Some in the scientific community believe the reason amyloid therapies have failed so far is because too little of the therapy was given, and too late. The jury is still out," said Rosenberg in the press release.

Rosenberg expects the new DNA vaccine will be tested further, given that treatments for early stage Alzheimer's disease have priority in the FDA's initiative.

Then, he believes he may be able to solve the question of whether amyloid is a vital target for preventing or curing Alzheimer's disease.