Scientists at Johns Hopkins have demonstrated that a specific enzyme in the brain is essential for nerve cells to form a hallmark of Alzheimer's disease (AD) - the so-called amyloid plaques that collect and surround brain cells. While aging brains of apparently healthy people contain scattered amyloid plaques, the brains of AD patients are littered with them.
Last year, five research groups cloned the gene for the enzyme, called beta-secretase, but the Hopkins scientists say they are the first to show the enzyme is responsible for forming the molecules that comprise plaque within the brain's nerve cells. Beta amyloid - the plaque molecule - forms inside nerve cells, then is shuttled outside where it collects into plaques.
Beta-secretase is a topic of intense research interest for pharmaceutical and academic centers worldwide because it's one of two enzymes associated with plaque formation. Many scientists believe plaques are the probable trigger of AD's destruction in the brain. "Knowing this enzyme is the major player in forming plaques offers a way to tell if the structures truly are important in Alzheimer's. And if that's the case, the enzyme also offers a clear target for therapy," says research team member Philip Wong, Ph.D.
The research is scheduled for presentation at this year's meetings of the Society for Neuroscience in New Orleans.
In the Hopkins study, scientists knocked out the genes for beta-secretase in mice. They then cultured nerve cells from the animals' brains and, using antibodies targeted to beta-secretase, confirmed the enzyme wasn't present. As expected, the nerve cells lacking the enzyme failed to form beta amyloid, the plaque protein.
"The mice without beta-secretase genes are born apparently normal and seem to suffer no untoward effects, but we're watching the mice as they age," says Huaibin Cai, Ph.D., another of the researchers. "So far, at four months, the mice appear fine."