October 17, 1997

VUMC investigator closing in on second Alzheimer’s gene

VUMC investigator closing in on second Alzheimer's gene

A Vanderbilt University Medical Center researcher is homing in on a second gene that may play a role in controlling late-onset Alzheimer's disease.

The gene's precise location and true function have yet to be determined, but investigators say it could be responsible for between significant portion of cases involving the debilitating disease.

"This is an important step in the process of discovering exactly what the gene does. As of yet, we just know it is located in chromosome 12, but once it is identified then we can begin to investigate its function," said Dr. Jonathan Haines, associate professor of Molecular Physiology and Biophysics and the senior author of the study.

Results of this work, a collaboration between Vanderbilt and Duke University, were published in this week's issue of the Journal of the American Medical Association.

Previous studies located the APO-E gene on chromosome 19, which is thought to be responsible for up to 50 percent of Alzheimer's disease cases. This second gene is located somewhere in the genetic code of chromosome 12, which is thought to be responsible for 10-15 percent of Alzheimer's disease.

"We have a region that we think has a gene in it and now we have to find that gene. Once it is located the gene will provide us with all kind of information about how Alzheimer's disease comes about and could lead us to new treatments and perhaps a cure," said Haines.

Now that a chromosome has been identified, more detailed genetic mapping will be used to further narrow the search for the second Alzheimer's gene.

"Additional genetic screening will be used to compare the signposts, called genetic markers, on chromosome 12. We are hoping that these markers, will lead us to the gene that is responsible for the disease," said Haines.

Alzheimer's disease is a progressive degenerative disease that ultimately results in severe mental deterioration. It particularly affects the cerebral cortex and the hippocampus, areas involved in cognitive functions and memory.

Genetic markers like the one Haines is searching for act as a sort of chromosomal guide, telling scientists where to look for different genetic functions. The chromosomes are covered with genetic markers, allowing researchers to zero in on the section of the chromosome they want to look at.

Haines also used this technique to help find a gene that controls tuberous sclerosis, a disorder that causes benign tumors to form throughout the body. That work was published in the August issue of Science.

The gene, once cloned, could lead to gene therapy treatments to aid in the care of thousands of people afflicted by tuberous sclerosis.

Though tuberous sclerosis tumors are benign, they can cause massive problems when they develop in the brain, liver, or kidneys.

"This is a disease that is fairly common, it occurs in one in about 7,000 people. We have been searching for a long time to find the genes responsible for it," said Haines.

The first suggestion that the gene, TSC1, might be linked to chromosome 9 was made in 1985. Researchers have been searching for it ever since and have finally discovered what they believe to be the gene's responsibility.

With the gene's precise location revealed, scientists hope to devise a way to stop the formation of tumors in patients with the disorder.

"The current theory is that this gene is similar to cancer genes in that it controls cell growth functions, but that is only a theory and has not been proven. Now that we have located TSC1, other scientists can begin to discover how it causes tumor growth," said Haines.