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.