Peek inside brains may help decode Alzheimer's

Scientists for the first time have peered into people's brains to directly measure the ebb and flow of a substance notorious for its role in Alzheimer's disease.

The delicate research was performed not with Alzheimer's patients but with people suffering from severe brain injuries – because a brain injury increases the risk of developing dementia later in life.

The goal is to learn why, so doctors one day might be able to lower that risk.

But with this first-step study, a team of scientists from Missouri and Italy got a surprise.

Too much of that Alzheimer's-related protein, called beta-amyloid, is thought to be harmful. So the team had expected beta-amyloid levels to spike right after the injury, then drop as patients recovered.

Instead, beta-amyloid levels rose as patients improved and fell if they got worse, lead researcher Dr. David Brody, a neurologist at Washington University in St. Louis, reported today in the journal Science.

What's going on? Beta-amyloid seems to be a marker of increased brain activity as patients improve.

If so, what started as a study of Alzheimer's risk might have implications for how the brain-injured are tracked in intensive-care units.

“Our study is just the beginning,” Brody said. “Amyloid-beta measurements in the brain may turn out to be a good indicator of how well the cells are communicating with each other.'

Beta-amyloid is best known as the goo that makes up the hallmark plaques in the brains of Alzheimer's victims. But it doesn't start as gunk. Soluble forms are in the fluid that bathes the brain, but scientists don't understand its purpose, or what happens to trigger formation of those bad plaques.

Nor do they understand why brain trauma so often leads to later Alzheimer's. One possibility is that extra beta-amyloid speeds whatever dementia-forming process might be lurking among brain cells. Another theory is that the injury decreases a person's “cognitive reserve,” so symptoms merely become apparent sooner.

Brody thought brain-injured patients could offer a precious chance to test that first possibility. Patients were having brain surgery, anyway. What if surgeons could insert an extra tube that would allow hour-to-hour sampling of brain fluid, to measure beta-amyloid?

It's a technique called intracerebral microdialysis, and colleagues at Washington University already had performed it in mice – linking increased synaptic activity, or communication between brain cells, to increased beta-amyloid.

Brody teamed with Dr. Sandra Magnoni of the Ospedale Maggiore Policlinico, a major trauma center in Milan with experience in the technique. They invited families of patients with brain injuries from car crashes, falls or hemorrhages from burst blood vessels to agree to the experiment. Eighteen said yes.

While the work raises more questions than it answers, it brings a valuable new tool for studying both Alzheimer's risk and just what happens during brain-injury recovery.