Anti-Alzheimer's Vaccine

By William K. Summers, MD
© 2001-William K. Summers, MD

What if you could prevent Alzheimer's with a vaccine? Like preventing smallpox? Today there is a buzz in the science community about just that.

For the past decade, neuroscientists have pursued the ß-amyloid theory of Alzheimer's disease. Since the 1920s, it has been known that the abnormal waxy deposits in the brains of Alzheimer victims is amyloid. In the 1980s it was further determined this was ß-amyloid. This protein, is a large insoluble molecule. Proteins are made up of strands of up to hundreds of amino acids. Because this is the same molecule seen in Down's Syndrome, Alzheimer's was suspected to be a genetic illness. In the 1990s, a small fragment of 40 to 42 amino acids within ß-amyloid caused the toxic death of nerve cells. Scientists hypothesized that abnormal genes resulted in abnormal ß-amyloid. The abnormal protein could not be cleared out of the brain. These deposits grow with age. The deposits kill nerve cells. Hence, Alzheimer's is genetic.

The search for these abnormal genes has not panned out. Because Harvard and several major universities were behind the research, there was much publicity. The seven current abnormal genes known to cause dementia have been found in less than 500 humans world wide. Only five hundred in over sixteen million world wide cases of Alzheimer's disease. Direct genetic involvement in Alzheimer's disease is rare. Recently, the shift has been to treatments that somehow alter the production or breakdown of ß-amyloid.

In the past three years, Elan Pharmaceuticals of South San Francisco has developed genetically altered mice. These mice deposit huge amounts of ß-amyloid in their brains from an early age. With this model, Elan scientists developed a vaccination. It is said to reduce the ß-amyloid load of the mouse brain. This is done by injecting (vaccinating) ß-amyloid back into the transgenic mice. Theoretically, the injected ß-amyloid causes microglia (scavenger cells in the brain) to activate. The microglia suddenly become interested in the deposits of naturally occurring ß-amyloid. The microglia began to "eat" the ß-amyloid plaques. The micorglia process the this waxy material. The excess ß-amyloid is moved to the blood and out of the body. Elan, and many scientists maintain that removal of the ß-amyloid will improve memory and work toward curing Alzheimer's.

These data were presented at the World Alzheimer's Congress in Washington DC this last July. They also presented almost a full day of data on the project at the Neuroscience Meetings in New Orleans in November 2000.

I was present for both presentations. I believe it is a bit premature to declare a cure from this process.

One of the early problems, was that the transgenic mice had brains loaded with ß-amyloid but did not display memory deficits. In the presentations of year 2000, effort was made to show in some cases, the transgenic mice showed learning and memory problems. One presenter went to great lengths to strengthen the belief that the altered mice have memory difficulties. The methods used to establish this, however, were substantially different from the standard methods. Nonetheless, by their method, repeated vaccinations resulted in better memory performance in these mice.

The lack of neurofibillary tangles is a second problem. Tangles are the other hallmark of Alzheimer's disease. These transgenic mice do not develop neurofibillary tangles. So the mice do not have Alzheimer's Disease. Third, why should external injections of ß-amyloid interest microglia. Piles of the stuff already surround the micorglia, but do not activate the microglia. Fourth the long-term safety of injecting a brain protein repeatedly to stimulate autoimmune response is not established.

Short-term safety studies have been done on the vaccine in humans. Elan is ready to begin human testing. Soon there will be studies available for victims of Alzheimer's to join. This is good news. Whatever the result, the frontier of knowledge will be pushed back.

With this kind of research energy, I do believe that we will have a cure for Alzheimer's disease within the next decade.

To your health.