Vaccine may clear Alzheimer’s brain plaques

While there is still no consensus about the role of waxy amyloid plaques that fill the brains of Alzheimer’s patients, many in the field believe they are a root cause of neurodegeneration and that clearing them may improve the cognitive function of patients. A major strategy has been to remove amyloid-beta by creating antibodies against it. But trials for an amyloid-beta vaccine were halted in 2003 when 6 percent of the patients developed life- threatening encephalitis. Since then, two follow-up studies provided some evidence that patients did benefit, raising hopes that a vaccine may work if side effects are limited. Another trial is under way to see if delivering amyloid-beta antibodies, rather than the peptide itself, can be effective and safer.

In the September 2005 Journal of Clinical Investigation, a team led by Howard Weiner, the Robert L. Kroc professor of neurology at Harvard Medical School and Brigham and Women’s Hospital, unveiled another vaccine strategy for Alzheimer’s disease that clears the build-up of amyloid plaques in a mouse model. The new strategy triggers cells of the immune system to gobble up amyloid-beta, sidestepping antibodies completely. It is delivered as a simple nasal spray, and consists of two FDA-approved drugs already in use for other conditions.

The vaccine emerged from a fortuitous discovery during an investigation of the role of the immune system in Alzheimer’s. After the problems with the amyloid-beta vaccine, Weiner worked with postdoctoral fellow Dan Frenkel and Ruth Maron, assistant professor of neurology at BWH, to investigate the relationship between Alzheimer’s and an overactive immune system that would produce encephalitis.