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Alzheimer’s Vaccine
December 20, 2000
Ronald Reagan
image: Elan Corporation

For the more than four million Americans who suffer from Alzheimer’s disease, the news last year of a vaccine in mice that could stop the formation of plaques in the brain associated with the disease offered new hope. But some scientists wondered if the vaccine might do more harm than good.

Now two independent studies published in this week’s journal Nature show that when given to mice, the vaccine can halt the progression of memory loss—one of the major hallmarks of the disease.

Mouse trap

When they began their research, scientists at the University of South Florida were actually setting out to prove that the vaccine, developed last year by Elan Pharmaceuticals, would cause memory deterioration. They were concerned that it might provoke an immune response that could end up causing the very memory loss it was designed to prevent.

Mouse in water maze
The white mouse at the left side of this pool hasn’t found the hidden underwater platform (red arrow).
image: WSTF, Tampa

But the opposite turned out to be true. Researchers tested mice genetically engineered to develop Alzheimer’s disease to see how well they performed in a water maze using a hidden platform whose location they were required to learn. "All the mice we gave the vaccine to were able to learn this task, none of the mice that we did not give the vaccine to were able to learn this task," says David Morgan, lead author of the study. "So, not only did we not find what we thought we would find—that is, a premature memory loss—but we in fact found that the vaccine completely protected these mice from developing the memory loss that they otherwise would have."

To test whether the vaccine might cause memory loss, Alzheimer’s mice were tested after they’d been inoculated for several months but before memory deterioration was expected to begin (11.5 months). They performed as well as controls. When they were tested at 15.5 months (roughly equivalent to a person in his or her early 60s) however, an age when they would have been expected to have memory deficits, they still didn’t show any, whereas Alzheimer’s mice that were not vaccinated did show such a loss.

Scientists at the University of Toronto reported similar results. Using a different mouse model and different timing of the vaccine, researchers led by Peter St. George-Hyslop reported improved memory in vaccinated mice with the Alzheimer’s gene.

It’s not brain surgery

Slide showing ß-amyloid plaques in mouse
ß-amyloid deposits are seen as brown spots in the mouse brain tissue on the left. The deposits were eliminated by treatment with the vaccine as seen on the right.
image: Elan Corporation

The vaccine, developed by Dublin-based Elan Pharmaceuticals, caused quite a stir when it was first reported in Nature in July, 1999. It was shown to prevent the build-up of amyloid plaques—protein fragments that form sticky buildup in the brains of Alzheimer’s patients—in mice engineered to have the disease. Along with neurofibrillary tangles, amyloid plaques are thought to cause damage to neurons in the brain and thus lead to the symptoms of Alzheimer’s disease.

Although the vaccine began to be tested in humans last year, Elan had no way of knowing whether it actually reduced memory loss in the mice, or just helped eliminate plaques. There was even a chance it could worsen the disease.

Because the vaccine consists of an injection of the same protein—beta amyloid—that causes the plaques in the first place, Morgan and other scientists were concerned that it might cause an immune reaction that could lead to inflammation that would kill brain cells. In fact, it is not known whether Alzheimer’s symptoms are caused by the plaques themselves or the immune system’s reaction to beta amyloid.

"We thought that the vaccine itself would be something you shouldn’t be putting into human beings," says Morgan. "We wanted to demonstrate with our mouse model that it caused a premature memory loss, that this loss of memory would in fact be indicative that activating the immune system in the brain is not something that you want to do."

Morgan says he was prepared to try and halt the human trials, but now favors them. Last July, Elan reported at the World Alzheimer’s Congress that trials in humans have so far shown the vaccine to be safe. Those wanting to enter clinical trials should be aware that while some patients could be the first to experience the benefits of the new vaccine, others will receive a placebo, which has no effect.

If the thought of a needle is less than appealing, new research has shown that there may be other ways to deliver the vaccine. Researchers at Harvard Medical School reported that a nasal vaccine against Alzheimer’s tested in mice could also reduce amyloid plaques. The results were published in the October issue of Annals of Neurology. While the nasal application, which works like an asthma or allergy inhaler, was not quite as effective as the injections, it may prove to be easier to administer in the long term.

The next step, at least for Morgan, is to find out if the vaccine can reverse memory loss. By testing Alzheimer’s mice at 15 months to show that they have already developed memory loss, vaccinating them for several months, and then retesting them, he expects to be able to tell if the loss has been reversed. "If we’re able to do that, I’ll be flabbergasted," says Morgan. "That will tell me that this treatment really is a true miracle in the possible treatment of Alzheimer’s disease."

Elsewhere on the web

National Institute on Aging’s Alzheimer’s Disease Centers Program Directory

Alzheimer’s Disease Clinical Trials Database

Alzheimer’s Disease Education Referral Center

NIH 1999 Progress Report on Alzheimer’s Disease

The Brain and Alzheimer’s Disease

by Jill Max

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