It's a simple idea: Inject a weakened form of a virus or bacteria into a person and allow his or her immune system to mobilize against it. That person is then protected against developing the disease caused by that microorganism. It has worked for many other diseases, from polio to measles–why not for Alzheimer's?
A team of scientists at Elan Pharmaceuticals recently tried that idea (Schenk et al., 1999). They developed a partial transgenic mouse model of AD by inserting the human mutated gene for APP into the mouse's DNA. The mice made the mutated protein and developed amyloid plaques as they grew older. The researchers were then able to use this mouse model to test whether any treatment had an effect on plaque buildup. Their next step was to construct a vaccine composed of beta-amyloid and a substance known to excite the immune system. In a first experiment, they gave one group of transgenic mice monthly injections of the vaccine starting at 6 weeks of age and ending at 11 months. A second group of transgenic mice received no injections and served as a control group. By 13 months of age, the mice in the control group had plaques covering 2 to 6 percent of their brains. In contrast, the immunized mice had virtually no plaques.
In a second experiment, the researchers began the injections at 11 months, when some plaques had already developed. Over a 7-month period, the control transgenic mice had a 17-fold increase in the amount of plaque in their brains, whereas those who got the vaccine had a 99-percent decrease compared to the 18-month-old control transgenic mice. In some mice, some of the pre-existing plaque deposits seemed to have been removed by the treatment. The team also found that other plaque-associated damage, such as inflammation and abnormal nerve cell processes, lessened as a result of the immunization.
This is a preliminary study in mice and much work needs to be done to follow up on and reproduce this research. For example, scientists need to find out whether vaccinated mice remain healthy in other respects and whether memory of those vaccinated remains normal. Furthermore, because the mouse model is not a complete representation of AD (the animals do not develop neurofibrillary tangles nor do many of their neurons die), additional studies will be necessary to determine whether humans have a similar or different reaction from mice. Another issue to consider is that although amyloid deposition is common to all human AD cases, the mutant APP gene is only directly responsible for a small percentage of early-onset AD cases. This means that the method may work on only some people. It may perhaps "cure" amyloid deposition but fail to stop development of dementia. Technical issues present challenges as well. For example, scientists will need to see whether it is even possible to create a vaccine that enables people to raise antibodies against their own proteins. Issues of safety and effectiveness also will need to be resolved before any tests in humans can be considered.
Despite all these caveats and challenges, this study represents a major conceptual and scientific advance and it could be the beginning of a huge step forward in AD treatment. This study builds on the tremendous body of work supported by the Federal Government over the last 20 years, and more recently, by pharmaceutical companies. Without this investment, this research would not have been possible. If this technique works, it is possible to consider that AD, a disease predicted to cripple the health care system in the next century, could be cured. Even if this exact technique does not work, it may still lead to entirely new immunological approaches to blocking amyloid deposition in AD and other neurologic diseases as well.
Source: National Institutes of Health; National Institute on Aging
1999 PROGRESS REPORT ON ALZHEIMER'S DISEASE