6 January 2009
column
Lagos — A slow, chronic starvation of the brain as we age appears to be one of the major triggers of a biochemical process that causes some forms of Alzheimer's disease.
A new study from Northwestern University's Feinberg School of Medicine has found when the brain doesn't get enough sugar glucose as might occur when cardiovascular disease restricts blood flow in arteries to the brain.
Robert Vassar, lead author, discovered a key brain protein is altered when the brain has a deficient supply of energy. The altered protein, called elF2alpha, increases the production of an enzyme that, in turn, flips a switch to produce the sticky protein clumps. Vassar worked with human and mice brains in his research. The study is published in the journal Neuron.
"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," said Vassar, a professor of cell and molecular biology at the Feinberg School.
A simple preventive strategy people can follow to improve blood flow to the brain is getting exercise, reducing cholesterol and managing hypertension.
"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.
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.
The disease usually begins after age 60, and risk rises with age. Ten years ago, it was Vassar who 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 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.
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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