Without Plaques, Alzheimer's Mice Recover

The brain cells in a mouse model of Alzheimer's disease (AD) recovered rapidly after the characteristic brain plaques were removed, according to a new study conducted by researchers at Washington University School of Medicine (St. Louis, MO, USA).

The researchers injected the mice with an antibody for a key component of brain plaques, the amyloid beta (Abeta) pepide. In areas where the antibodies cleared the plaques, many of the swellings observed on nerve cell branches rapidly disappeared. Prior to the experiment, many scientists believed plaque damage to nerve cells was something that only needed to happen once. The new findings suggest that the plaques might not only cause damage but also actively maintain it.

The mice used in the study had two mutations. One caused amyloid plaques to build up, while the second caused some of the mouse brain to produce a dye that allowed researchers to obtain detailed images of nerve cell branches. To correlate brain cell changes with plaque development, another dye was injected that temporarily sticks to amyloid. As the plaques appeared, nearby branches of nerve cells developed bumps and swellings. The swellings make it difficult or impossible for nerve-cell branches to send signals.

After showing that the number and size of the swellings were stable over the course of three to seven days, the Abeta antibodies were injected directly on the surface of the mouse brains. The plaques were cleared, and the swellings were monitored for three days. By then, there were no new swellings and there were 20-25% reductions in the number and size of the existing swellings. The largest swellings were least likely to heal.

"This provides confirmation of the potential benefits of plaque-clearing treatments and also gets us rethinking our theories on how plaques cause nerve-cell damage,” commented David H. Holzman, M.D., professor and head of the department of neurology at Washington University School of Medicine. The results of the study appear in the February 5, 2005, issue of the Journal of Clinical Investigation.




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