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Antibody may hold key to treatment of Alzheimer's, strokes

In research with mice, an experimental drug was shown to clear amyloid plaques, linked to the development of Alzheimer's disease, from the brain without dangerous side effects. File Photo by Riff/Shutterstock
In research with mice, an experimental drug was shown to clear amyloid plaques, linked to the development of Alzheimer's disease, from the brain without dangerous side effects. File Photo by Riff/Shutterstock

Feb. 17 (UPI) -- Researchers at Washington University in St. Louis said Wednesday that they have discovered an antibody that removes harmful brain plaques associated with increased risk for Alzheimer's disease and strokes.

The antibody targets a specific protein that is a key component of amyloid plaques that form on the brain as people age, the researchers said in an article published by Science Translational Medicine.

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The plaques are seen as the first step on the path to Alzheimer's dementia and, when they form around blood vessels in the brain -- a condition known as cerebral amyloid angiopathy -- they also raise the risk of strokes.

The finding that the antibody, called HAE-4, may provide a gateway to drug treatments for both conditions, without the dangerous side effects associated with other approaches being studied, including brain swelling and bleeds.

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Antibodies are proteins produced by the human immune system to fight off dangerous pathogens, and anti-amyloid antibodies work by alerting the immune system to the presence of unwanted material, such as amyloid plaques.

"Alzheimer's researchers have been searching for decades for therapies that reduce amyloid in the brain, and now that we have some promising candidates, we find that there's this complication," study co-author Dr. David Holtzman said in a press release.

"We've taken a different approach ... and it seems to be effective at removing amyloid from both the brain tissue and the blood vessels, while avoiding this potentially dangerous side effect," said Holtzman, a professor of neurology at Washington University.

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In recent years, several antibodies that target amyloid plaques have been studied as experimental treatments for Alzheimer's disease. Amyloid plaques in brain blood vessels are dangerous because they can lead to blockages or ruptures that cause strokes.

To determine whether HAE-4 removes amyloid from brain blood vessels without the side effects, Holtzman and his colleagues used mice genetically modified with human genes for amyloid and APOE, which has been associated with the development of cognitive impairment.

After eight weeks of treatment with HAE-4, the mice had reduced amyloid plaques in their brain tissue and brain blood vessels, the researchers said.

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Treatment also significantly improved the ability of brain blood vessels to dilate and constrict on demand, an important sign of vascular health.

"A buildup of amyloid in brain blood vessels can be managed by controlling blood pressure and other things, but there isn't a specific treatment for it," Holtzman said.

"This study is exciting because it not only shows that we can treat the condition in an animal model, but we may be able to do it without the side effects that undermine the effectiveness of other anti-amyloid therapeutics," he said.

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