Gene for Alzheimer's Risk May Affect Brain Early

Study Shows Young Adults With Gene Show Signs of Changes in the Brain

By Kathleen Doheny
WebMD Health News

Reviewed by Laura J. Martin, MD

May 18, 2011 -- Young adults who carry a so-called Alzheimer's risk gene show disruption in their brains as early as their 20s, according to new research.

Researchers from the University of California, Los Angeles used a special MRI scan that maps brain connections to examine 398 healthy young adults. Some carried the variant of the gene linked with Alzheimer's risk and some did not.

"The people who carry this gene have severely impaired wiring in most of their brain, even when they are young," says researcher Paul M. Thompson, PhD, professor of neurology at the University of California, Los Angeles David Geffen School of Medicine.

Even so, they don't notice symptoms of Alzheimer's disease, such as memory loss at this time, he tells WebMD. Following a healthy lifestyle early can offset the genetic risk, he says.

The study is published in The Journal of Neuroscience.

Genetic Link to Alzheimer's Disease

For late-onset Alzheimer's disease, which appears in old age, scientists know there is a strong genetic link.

In 1993, scientists discovered the gene known as ApoE4, carried by about 25% of people. It triples the risk of Alzheimer's disease.

Then, in 2009, scientists found more ''risk'' genes. One is called clusterin or CLU. Those who have the CLU gene form known as CLU-C have about a 16% higher risk of Alzheimer's disease than those who have the CLU-T gene form.

However, the experts who discovered the new risk gene could not say why it boosted the risk. "This is the first clear evidence of what it does," Thompson tells WebMD.

About 88% of whites carry the CLU-C variant, Thompson says.

He used a special MRI scan to look closely at the brain's connections. Among the 398 people scanned, some had one copy of the CLU-C variant, some had two, and some had none.

"We basically wanted to see how the people who carry this gene differ," Thompson tells WebMD.

They found the CLU-C carriers had what scientists call lower ''fractional anisotropy." This is a measure of white matter brain tissue integrity. ''The white matter integrity was about 10% lower in the carriers of the gene compared to the ones who didn't have it," he says. Those who carried two copies of CLU-C had even lower white matter integrity, he says.

The findings suggested that the change in the white matter was due to reduced integrity of the myelin, the protective coating covering the brain cells.

The study suggests the gene variant ''does its work very early," Thompson says. And it does so, he says, not by forming the plaques associated with Alzheimer's disease but by damaging the myelin, the protective coating on the brain's nerve cells.

It's known that in Alzheimer's disease, the white matter pathways deteriorate due to impaired myelin and other factors.

Alzheimer's Risk Is 'Minor'

The study findings are unique but also preliminary, says Charles DeCarli, MD, professor of neurology at University of California, Davis. He reviewed the study for WebMD but was not involved in the research.

He agrees that the study provides the first clear evidence of what the gene variant does to the brain.

While the gene variant is widespread in the population, people should not be unduly alarmed, he says. "This is a perfect example of what we we call a susceptibility factor." In the big picture, "it is a very minor risk factor for Alzheimer's."

"The idea here, if we confirm it, is that this is probably a susceptibility factor, that the myelin is somehow more vulnerable and it is somehow more vulnerable to any brain disease," says DeCarli, who directs the university's Alzheimer's Disease Center.

"It is furthering our understanding of many risk factors that lead to potential cognitive impairment as we get older and that make us more vulnerable to Alzheimer's disease," he says.

Lifestyle Tips for Brain Health

The new research shouldn't make people anxious, Thompson agrees.

Rather, he hopes it motivates people to improve or maintain a healthy lifestyle. "You can more than erase the hit this gene gives you," he says.

There are proven ways to protect brain health, he says, including:

  • Engaging in cardiovascular exercise
  • Eating a healthy, low-fat diet
  • Stimulating the brain by learning something new or traveling


One of the first symptoms of Alzheimer's disease is __________________. See Answer

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SOURCES: Braskie, M. The Journal of Neuroscience, May 4, 2011; vol 31: pp 6764-6770.Paul M. Thompson, PhD, professor of neurology, University of California, Los Angeles David Geffen School of Medicine.Charles DeCarli, MD, professor of neurology; director, Alzheimer's Disease Center; director, Imaging of Dementia and Aging Lab, University of California, Davis. ©2011 WebMD, LLC. All Rights Reserved.