Antibody Helps Reverse Alzheimer's Nerve Damage

Mouse study shows brain cells can recuperate after plaques are removed

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HealthDay Reporter

THURSDAY, Jan. 20, 2005 (HealthDayNews) -- Scientists have discovered that an experimental plaque-clearing antibody given to mice with Alzheimer's disease not only halts nerve damage in the brain but actually reverses some of it.

The study, led by Dr. David H. Holtzman of Washington University School of Medicine in St. Louis, may energize the race to develop a human treatment for Alzheimer's.

Drug developers are focusing on ways to prevent or reduce the build-up of amyloid-beta (Abeta) protein in the brain -- a hallmark of the disease. Those sticky plaques are believed to cause surrounding nerve cells to develop abnormal swellings, or neuritic dystrophy. Until now, no studies had demonstrated the actual effect of plaque-clearing treatments on the nerve cells or the progression of the disease.

"Holtzman and colleagues provide the first evidence that dystrophy is reversible, and that reversibility can be induced with anti-amyloid antibody," said Dr. Samuel Gandy, director of the Farber Institute for Neurosciences of Thomas Jefferson University in Philadelphia, and vice chairman of the National Medical and Scientific Advisory Council of the Alzheimer's Association.

The findings appear in the Feb. 1 issue of the Journal of Clinical Investigation.

Alzheimer's disease (AD) is a progressive brain disorder that eventually destroys a person's memory and abilities to learn, reason, communicate and perform daily activities. Some 4.5 million Americans suffer from it, and by 2050, the number could swell to between 11.3 million and 16 million, the Alzheimer's Association reports.

"One of the predominating hypotheses in the AD field is that Abeta peptide is a major contributor, if not the cause, of the onset and the progression of the disease," said lead author Robert Brendza, a research instructor in neurology at Washington University School of Medicine.

This study, he explained, was meant to provide scientific confirmation that altering amyloid plaques in the brains of mice can elicit a change in nerve damage.

To test the theory, Brendza and his colleagues monitored changes that occurred in live brain cells of mice genetically engineered to develop plaques and neuritic dystrophy and bred to produce a dye that let the researchers obtain detailed images of nerve cell branches. Another dye, a yellow fluorescent protein that sticks to amyloid, was injected in the mice to track brain cell changes.

After showing that the swellings in the nerve cells were mostly stable in number and size over a period of three to seven days, the investigators applied an antibody treatment directly to the surface of the mouse brains, and then they watched to see what would happen.

"Over a three-day period, you do get significant clearance of Abeta deposits, and in that same three-day period we saw like a 20-to-25 percent reduction in the number and size of (the swellings)," Brendza said.

This shows that Abeta deposits are responsible for the nerve damage that occurs in Alzheimer's disease and that some of the nerve damage depends on the continued presence of amyloid beta, he explained. What's more, it shows that at least some of this Abeta-induced nerve damage is reversible.

"It's promising, but it's not the end all, because the thing is we really don't know if all of this nerve damage is reversible," Brendza added. "We know some of it is."

While the study suggests that removing sticky deposits may have at least some benefit, more research is needed to determine whether the approach has similar effects in humans.

More information

The Alzheimer's Association has a fact sheet on beta-amyloid.

SOURCES: Robert Brendza, Ph.D., research instructor, Department of Neurology, Washington University School of Medicine, St. Louis; Samuel Gandy, M.D., Ph.D., director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, and vice chairman, National Medical and Scientific Advisory Council, Alzheimer's Association, Chicago; Feb. 1, 2005, Journal of Clinical Investigation

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