From Mice to Men: New Hope for Treating Alzheimer's Disease

By Ellen Kuwana
Neuroscience for Kids Staff Writer
August 12, 1999
Alzheimer's disease (AD) has no cure. In fact, very little can be done to slow the progression of the disease. At this time, health care professionals can only treat the symptoms, hoping to make patients and their families more comfortable with the patient's inevitable loss of abilities. Some drugs, such as Tacrine and Aricept, have been shown to lessen the symptoms of AD, but neither drug slows the progression of the disease.

The causes of AD are unclear. It is known that the disease causes changes in the brain. However, it is not known whether these changes, such as the buildup of a protein called beta amyloid, contribute to the decline in mental functioning in AD patients, or whether the changes are a by-product of the disease. Although much research has focused on helping Alzheimer's patients, this work has produced few treatment options, and none even approach a cure.

New Hope

In July 1999, a team of scientists headed by Dale Schenk reported that they had harnessed the immune system to fight AD (Nature, Vol. 400, July 8, 1999). Because this novel approach to treating AD uses the body's own defenses to fight the disease, it is being called a "vaccine." This research is important because it demonstrates that a vaccine may be used to fight a disease caused by a substance from your own body (in this case, protein deposits). Other vaccines have targeted foreign substances, such as polio or chickenpox viruses or tetanus bacteria.

How does this vaccine work?

Your immune system is at work all the time, sending immune cells to fight bacteria, viruses, and other invaders in your body. But some harmful substances escape your body's defense system. A protein called beta amyloid is naturally found in the body. However, in AD brains, this sticky protein clumps together to form plaques, a feature that can be seen when the brain is examined. These plaques may or may not contribute to the decline of cognitive abilities in AD patients. Until now, there was no way to investigate their role in AD to see if they were damaging the brain or were merely innocent bystanders.

Exciting the Immune System to Fight Amyloid Plaques

The researchers took advantage of the immune system's defense properties and taught it to recognize beta amyloid as an unwanted invader. This is like teaching a guard dog a new trick. They created a "vaccine" that combined beta amyloid with a substance that mobilizes the immune system. This vaccine caused the immune system to mount an attack against beta amyloid, which in turn reduced the number of plaques in the brain. (It's as if you were baking cakes and someone took away some of your batter. You wouldn't be able to bake as many cakes and each cake would not be as big.)

What is truly exciting about the results from this study is that the vaccine not only prevented further plaque formation, but it reduced the amount of existing plaques!

Testing the Vaccine, Experiment #1

How did the scientists test the vaccine? In a good experiment, there is a control group and an experimental group. The control group serves as a comparison for what happens in the experimental group. The experimental group receives a new treatment, whereas the control group does not. The two groups are treated identically in all other ways.

In the AD vaccine experiment, young mice (6 weeks old) were genetically engineered to produce lots of amyloid protein, more than normal mice would produce. Mice at this age have very few brain changes, such as plaques formation, associated with AD.

The experimental group received the "vaccine" of beta amyloid plus an immune system stimulator. The control group received everything except the beta amyloid. For 11 months, each group received one injection per month. When the scientists examined the mice brains, the control group had plaques covering 2-6% of their brains, while the group who received the "vaccine" had very few plaques. So the vaccine "essentially prevented the development of beta amyloid plaque formation," the report in Nature states. What's more, beta amyloid production was unaffected. This means that either the protein was being prevented from clumping into plaques, or it was being cleared out of the brain more effectively.

Testing the Vaccine, Experiment #2

At this point in the study, the researchers were interested in the effect of the vaccine on plaques already in the brain. This led to the second experiment, in which older mice were used.

For this experiment, researchers used mice who were old enough to have developed plaques (11 months old). Again, each mouse got an injection (either of vaccine or just the immune stimulator) once a month. Half of the mice from each group were examined after four months of treatment (15 months) and the other half after seven months of treatment (18 months). The results here were surprising and stunning. The control group had a 17-fold increase in plaques! The experimental group, the mice who had received the "vaccine," not only developed fewer plaques, but what plaques they had at 11 months were reduced at the 18-month point! This means that not only did the vaccine prevent further plaque formation, it reduced existing plaques, too! Because the goal of the vaccine was to decrease the amount of beta amyloid in the brain (and the numbers of plaques), the lower numbers here show that fewer plaques were seen in the brain. The vaccine appeared to have worked!

What needs to be done now?

  1. Is the vaccine toxic and are there side-effects?
    There were no signs of toxicity over the time period studied in the mice. Nevertheless, scientists will have to check if there are long-term side-effects in the mice. Then studies will be performed on humans after an extensive approval process. Concerns such as toxic side effects need to be addressed.

  2. Can the immune response that fights the beta amyloid protein be sustained?
    Getting the immune system to battle something that's not really foreign to our bodies is difficult. This is, for example, why the immune system fails to fight some cancerous tumor cells. If all goes well, the U.S. Food and Drug Administration will be asked to approve this treatment as a human vaccine.

  3. What is the role of plaques and tangles?
    In Alzheimer's, plaques are not the only abnormality in the brain. Neurofibrillary tangles also play a role in the disease process. Scientists do not know how plaques and tangles each contribute to the disease. If tangles turn out to cause most of the damage, being able to reduce plaques may not help treat the disease in humans.

  4. Will the vaccine work in humans?
    This research was performed using laboratory mice. It is unknown whether the same approach will work for humans. Although mice develop amyloid plaques just like AD patients, the mice do not show symptoms like AD so one cannot say that AD in mice has been cured. One can only say that the amount of plaques was reduced. But this work promises to steer Alzheimer's research in a new direction.

Even if the vaccine does not end up being the answer, it is an important piece in the Alzheimer's puzzle. Any news is good news for a disease with no cure, because science builds on known information. It's solving a mystery: each new piece of information leads researchers closer to the answer.


  1. Schenk, D., et al., Nature, July 8, 1999, pp 173-177. "Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse."
  2. Cowley, G., Newsweek, July 19, 1999, Outsmarting Alzheimer's
  3. Knight, J., New Scientist, July 10, 1999. Clearing the Mind.
  4. Manier, J., Chicago Tribune, July 8, 1999, "Discovery Could Lead to Alzheimer's Vaccine."

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