Dec 27, 2008

Health - Slow Starvation of Brain Triggers Alzheimer's

A slow starvation of the brain over time is one of the major triggers of the biochemistry that causes some forms of Alzheimer's, according to a new study that is helping to crack the mystery of the disease's origins.

An estimated 10 million baby boomers will develop Alzheimer's in their lifetime, according to the Alzheimer's Association. The disease usually begins after age 60, and risk rises with age. The direct and indirect cost of Alzheimer's and other dementias is about $148 billion a year.

Robert Vassar of Northwestern University, the study's lead author, found that when the brain doesn't get enough of the simple sugar called glucose - as might occur when cardiovascular disease restricts blood flow in arteries to the brain - a process is launched that ultimately produces the sticky clumps of protein that appear to be a cause of Alzheimer's.

Working with human and mice brains, Vassar discovered that a key brain protein is altered when the brain's supply of energy drops. The altered protein, called eIF2alpha, increases the production of an enzyme that, in turn, flips a switch to produce the sticky protein clumps.

"This finding is significant because it suggests that improving blood flow to the brain might be an effective therapeutic approach to prevent or treat Alzheimer's," Vassar said.

The best ways to improve blood flow to the brain and thereby reduce the chances of getting Alzheimer's is to reduce cholesterol intake, manage high blood pressure and exercise, especially entering mid-life.

"If people start early enough, maybe they can dodge the bullet," Vassar said. For people who already have symptoms, vasodilators, which increase blood flow, may help the delivery of oxygen and glucose to the brain, he added. The study is published in the Dec. 26 issue of the journal Neuron.

No candy bars

When it comes to prevention of Alzheimer's, eating candy bars is not the solution to improving the flow of blood glucose to the brain, Vassar told LiveScience.

A decreasing blood flow to the brain happens over time, as we age, and that slowly starves the brain of glucose. This could be a general aging phenomenon, or it could be that some individuals are particularly prone to it, Vassar said. Also, decreased blood flow is associated with atherosclerosis, or hardening of the arteries, and hypertension, or high blood pressure.

"We need to improve our cardiovascular health, not eat more sugar," Vassar said. "What is coming out in terms of the epidemiological studies is that exercise during mid-life is one of the best prevention strategies for Alzheimer's disease, so people should stay active physically, and they should watch their diets and reduce cholesterol intake, because cholesterol contributes to atherosclerosis, and that is true for the heart and the rest of the body as well as for the brain."

Vassar said it also is possible that drugs could be designed to block the elF2alpha protein that begins the formation of the protein clumps, known as amyloid plaques.

Earlier Alzheimer's findings

Ten years ago, Vassar discovered the enzyme, BACE1, that was responsible for making the sticky, fiber-like clumps of protein that form outside neurons and disrupt their ability to send messages.

But the cause of the high levels of the protein in people with the disease has been unknown. Vassar's new study now shows that energy deprivation in the brain might be the trigger starting the process that forms plaques in Alzheimer's.

Vassar said his work suggests that Alzheimer's disease may result from a less severe type of energy deprivation than occurs in a stroke. Rather than dying, the brain cells react by increasing BACE1, which may be a protective response in the short term, but harmful in the long term.

"A stroke is a blockage that prevents blood flow and produces cell death in an acute, dramatic event," Vassar said. "What we are talking about here is a slow, insidious process over many years where people have a low level of cardiovascular disease or atherosclerosis in the brain. It's so mild, they don't even notice it, but it has an effect over time because it's producing a chronic reduction in the blood flow."

Vassar said when people reach a certain age, some may get increased levels of the enzymes that cause a build-up of the plaques. "Then they start falling off the cliff," he said.

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