Tracking Alzheimer's-linked protein in live brains: whoops

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Tracking Alzheimer's-linked protein in live brains

By LAURAN NEERGAARD AP Medical Writer

08/28/2008

http://www.denverpost.com/healthcare/ci_10326269

WASHINGTON---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 severe brain injuries---because a brain injury

increases the risk of developing dementia later in life.

The goal is to learn why, so that 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 and then drop as patients recovered.

Instead, beta-amyloid levels increased as patients improved and dropped

if they got worse, lead researcher Dr. Brody, a neurologist at

Washington University in St. Louis, reported Friday in the journal Science.

What's going on? Beta-amyloid seems to be a marker of increased brain

activity as patients improved.

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---although that will take much more research to prove.

" 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 sticky goo that makes up the hallmark

plaques inside the brains of Alzheimer's victims. But it doesn't start

out as gunk. Soluble forms are found in the fluid that bathes the brain,

although scientists don't understand its purpose, or just what happens

to trigger formation of those bad plaques.

Nor do they understand how 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

that symptoms merely become apparent sooner.

Brody thought brain-injured patients could offer a precious opportunity

to start testing that first possibility. These patients were undergoing

brain surgery anyway. What if surgeons could insert an extra tiny tube

at the same time 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. Magnoni of the Ospedale Maggiore

Policlinico, a major trauma center in Milan that has experience with the

technique. They asked the families of patients suffering brain injuries

from car crashes, falls or hemorrhages from burst blood vessels if

they'd agree to the experiment. Eighteen said yes.

Roughly 24 hours after the initial injury, the catheter was placed in

patients' brains, where it stayed for three to seven days. ICU doctors

and nurses otherwise provided routine care, tracking patients'

neurologic changes with a standard tool called the Glasgow Coma Score.

Brody tracked the beta-amyloid levels and found they mirrored that coma

score, with a direct relationship to each patient's neurological status.

That means the findings agreed with the previous research on mice.

That's important, as so much Alzheimer's research must be performed in

animals, said Dr. Ramona Hicks, a specialist in traumatic brain injury

at the National Institutes of Health, which helped fund the work.

Brody cautions that beta-amyloid might have spiked in everyone right at

the time of injury, something his study started too late to measure.

Also, it only measured total beta-amyloid levels, not a strung-together

form that's thought to be toxic to cells, something Brody hopes to try next.

While the work raises more questions than it answers, it brings

researchers a valuable new tool for studying both Alzheimer's risk and

just what happens during brain-injury recovery.

" It sort of sets a platform for future studies, " said NIH's Hicks.