A Shot Against Alzheimer's?

Once largely limited to fighting infectious diseases, immunization may find a surprising new target. A report in tomorrow's Nature raises the startling possibility that physicians could someday immunize people to prevent, or even reverse, the mental devastation of Alzheimer's disease.

One early and consistent hallmark of Alzheimer's are protein build-ups in the brain, called plaques, made up of Ab42, an abnormal-length fragment of a normal cellular protein. While plaques haven't been proven to cause the symptoms, many researchers think they do. Several labs have bred transgenic mice that develop plaques, and although they don't develop the widespread neuron death and severe dementia seen in patients, they are used as models for research. Dale Schenk, vice president of neurobiology at Elan Pharmaceuticals in South San Francisco, wondered whether immunization with b amyloid (Ab) might produce antibodies that would prevent plaque formation in these mice.

When Schenk's team injected young mutant mice with Ab, they never developed plaque or neuron damage. When they immunized older mice that already had plaque in their brains, the plaque--and the signs of disease--largely vanished. In the brains of these mice the team found evidence of an immune response: bits of remaining amyloid that were dotted with antibodies, and microglia, the scavenger immune cells of the brain, chock-full of amyloid protein they had cleared away.

The finding "raises the possibility that immunization with Ab may eventually be used as a treatment, or prophylactically, for Alzheimer's disease," says Peter St. George-Hyslop, who studies the disease at the University of Toronto. "If so, this would be an absolutely tremendous result." Alzheimer's researcher Sam Sisodia of the University of Chicago agrees, but adds: "Things could work differently in humans."

Elan hopes to start clinical trials with the vaccine by the end of the year. Those trials could yield a verdict not only on this therapeutic approach but also on the importance of plaque in Alzheimer's disease. "The bottom line of this all," says St. George-Hyslop, is that "we will know quite clearly what the true role of extracellular Ab is in Alzheimer's disease. We will either get a brilliant treatment, or we will get some powerful insights that modify how we think about the disease."

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