Potential for a Vaccine against Alzheimer’s Disease?

Alzheimer’s is a progressive disease that is accompanied by dementia and severe loss of functioning. One of the physical hallmarks of this disease is the accumulation of plaques in the brain cells of patients and the loss of another protein (tau) that works to stabilize neural communication. Abnormal tau proteins lead to a tangling of nerve cells which increases the likelihood that the impacted brain cells will die off and eventually lead to memory loss and functional deficits.

New research demonstrates the possibility of a successful vaccination for Alzheimer’s Disease. This study tested an immunotherapeutic method that is designed to dissolve an existing protein called amyloid beta-peptide and/or interrupt their accumulation. Researchers were able to prevent the development of Alzheimer’s-related pathology in mice without causing significant side-effects.

The vaccinated mice generated an immune response to the amyloid beta protein, more commonly known as Alzheimer’s-related “amyloid plaques.” The mice in this study were able to develop an immune response despite being genetically designed to develop Alzheimer’s Disease. These findings are particularly encouraging because the mice were genetically engineered to create large amounts of amyloid plaque and to develop abnormal tau protein.
Alzheimers Plaque
The goal of the vaccine is to trigger an immune response in a way that forces the immune system to recognize the presence of amyloid beta-peptides. In this study, the researchers utilized the herpes virus, stripped of all viral genes that can cause harm. Then, they loaded the virus into a container containing the genetic code for amyloid beta and interleukin-4 which is a protein known to stimulate immune responses. Finally, they tested three different versions of the vaccine. First, the mice were injected with just the herpes virus alone. Next, they received an injection of a vaccine carrying only the amyloid plaque genetic code, and then finally a vaccine containing the amyloid plaque and interleukin-4.

In order to test the impact of these vaccines, the mice were trained to navigate a maze using spatial clues. They were then tested at multiple times during a 10-month period by tabulating the time and distance that each mouse was able to travel and counting the number of errors made. The mice were then examined for build up of amyloid beta-peptides and the proper function of tau protein.

The vaccine containing both the amyloid plaque and the interleukin-4 proved to be the most effective. Even more surprising was the finding that the these mice did not experience a transition from normal to abnormal tau functioning, which suggested that their memory had remained physically intact.

The researchers claim that these findings suggest they can create a safe and potent vaccine that utilizes the immune system to help prevent Alzheimer’s-related pathologies and memory deficits. However, further testing is required before this vaccine can be tested in humans. The researchers believe it could take up to three years or more before human testing begins.

Source: Frazer, M.E., Hughes, J.E., Mastrangelo, M.A. et al. 2008. Reduced pathology and improved behavioral performance in Alzheimer’s Disease mice vaccinated with HSV amplicons expressing amyloid beta and Interleukin-4. Molecular Therapy 16(5): 845-853.