Alzheimer's brain plaques cleared in mice
By Anthony J. Brown, MD
NEW YORK (Reuters Health) - Protein accumulations, or plaques, characteristic of Alzheimer's disease can be eliminated from the brains of mice, researchers report, by encouraging scavenger immune cells called macrophages to do their work.
The activity of macrophages is damped down by a naturally occurring compound called TGF-beta, to stop runaway reactions, and prior research has shown that brain levels of TGF-beta are increased in patients with Alzheimer's disease, according to the report in the research journal Nature Medicine.
Some researchers believed that the high levels of TGF-beta were simply an attempt to quiet the inflammatory response associated with Alzheimer plaques. However, the new findings contradict that notion.
The researchers genetically engineered mice to block TGF-beta signaling in macrophages in the peripheral circulation. They found that this "promotes the influx of these cells into brains of Alzheimer's mice," lead author Dr. Terrence Town, from Yale University School of Medicine in New Haven, Connecticut, told Reuters Health.
Remarkably, "this peripheral macrophage brain infiltration was actually therapeutic in these Alzheimer's mice," he said. "This surprised us because others have hypothesized that increasing immune responses in the brain may be deleterious by promoting inflammation, which can injure brain cells."
Up to 90 percent of brain plaques were eliminated in the genetically engineered mice, and the animals showed functional improvements, such as enhanced maze navigation.
"If our results translate to humans, it may be possible to administer a TGF-beta pathway blocking drug to the periphery, which would mobilize the peripheral macrophages to enter the brain and remove the senile plaques that build up in the brains of Alzheimer patients," Town said.
In line with this goal, he said, his team is now investigating drugs, rather than genetic strategies, that block TGF-beta.
SOURCEL: Nature Medicine, advance online issue May 30, 2008.