Researchers from Northwestern University's Feinberg School of Medicine have found that a slow, chronic starvation of the brain as people grow old appears to be one of the major triggers of a biochemical process that causes some forms of Alzheimer's disease.
While conducting a study with human and mice brains, they found that when the brain doesn't get enough sugar 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.
Lead author Robert Vassar 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.
"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 initial trigger of Alzheimer's has long been a mystery. Ten years ago, Vassar discovered the enzyme, BACE1, which was responsible for making the sticky, fiber-like clumps of protein that form outside neurons and disrupt their ability to send messages. However, 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.
"A stroke is a blockage that prevents blood flow and produces cell death in an acute, dramatic event. 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.
The study is published in the December 26 issue of the journal Neuron.