CHICAGO --- 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.
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 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.
This is good news and bad news. The good news is that a rejuvenating therapy for the vascular system will probably prevent Alzheimer's Disease. The bad news is that we might need a rejuvenating therapy for the vascular system to prevent Alzheimer's Disease.
Of course there are many things we can do dietarily and otherwise to slow the rate of decay of our veins and arteries. But all those good things to do just slow the decay. Very worth doing. But we still need the rejuvenating stem cells and gene therapy to fix up our piping.
Also, short of a rejuvenated circulatory system we can expect to see the development of therapies that block various steps involved in Alzheimer's development. But this result is an example of how the best strategy for attacking most of the diseases of old age is to reverse the aging process.
A team at U Rochester is chasing down what they think is a mechanism by which poor circulation turns on two proteins which block the removal of toxic amyloid beta.
"To some, it might seem odd that a cardiovascular group would intersect with a neuroscience group to study Alzheimer's disease," Miano said. "But there's a great deal of evidence to suggest that Alzheimer's disease is a problem having much to do with the vascular plumbing. And Rochester is the type of institution where partnerships like these are easy to strike up."
For 15 years Zlokovic's laboratory has focused on the molecular mechanisms regulating blood supply and the role of the blood-brain barrier in the development of Alzheimer's disease. It's not simply that reduced blood supply hurts brain cells by causing a shortage of oxygen and other nutrients. Rather, deterioration of blood flow seems to gum up the brain's ability to remove toxic amyloid beta.
These researchers have previously published results which suggest that a drug that blocks the proteins SRF and myocardin might improve brain blood circulation.
Two years ago, Zlokovic and Miano published a study showing that the two proteins are much more active in the blood vessels of brains of people with Alzheimer's disease than in people who do not have the disease. They showed that when they reduced the activity of the proteins, blood flow in the brain increased, and when the genes were more active, blood flow decreased.
The latest report goes further, implicating the molecular duo in the slowed removal of amyloid beta. The team found that SRF and myocardin working together turn on a molecule known as SREBP2. That protein inhibits a molecule known as LRP-1, which helps the body remove amyloid beta. In other words, when SRF and myocardin are active, toxic amyloid beta accumulates.
Now the team has turned its attention to studying the role of hypoxia, which seems to play a role in turning on myocardin, as well as searching for molecules that block the hookup between SRF and myocardin.
Even if these mechanisms become well understood and toxic protein accumulation becomes blockable with drugs our brains still need a circulatory system that works well enough to deliver sufficient sugar, oxygen, and other nutrients. Drugs that improve circulation are certainly within the realm of the plausible. But ultimately we still need rejuvenated circulatory systems.
|Share |||Randall Parker, 2008 December 24 10:08 PM Brain Alzheimers Disease|