Brain Starvation As We Age Appears To Trigger Alzheimer's: Improving Blood Flow To Brain Is Preventive Strategy

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ScienceDaily (Dec. 28, 2008) — 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 -- a

process is launched that ultimately produces the sticky clumps of protein that

appear to be a cause of Alzheimer's.

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 December 26 issue of 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.

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.

The initial trigger of Alzheimer's has long been a mystery.

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.

" 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.

Adapted

from materials provided by Northwestern

University, via EurekAlert!,

a service of AAAS.

http://www.sciencedaily.com/releases/2008/12/081224215704.htm