Originally created 12/13/01

Doctor seeks disease link in families' genes



The blood of some families afflicted by Alzheimer's disease is providing a spot of hope for finding a cause.

Medical College of Georgia researcher Shirley E. Poduslo recently located a spot, or locus, on chromosome 19 that is common to four large extended families afflicted by the disease.

Dr. Poduslo has worked to create a DNA bank, first at Texas Tech and now at MCG, of patients and families afflicted by late-onset Alzheimer's, which occurs after age 65.

Dr. Poduslo found the spot near a gene called APOE4 that already is known to be a risk factor for getting the disease, she said.

"We know that there's a gene on chromosome 19 called APOE4, and APOE4 is found in about 40 percent of Alzheimer's patients," Dr. Poduslo said. "We started looking in the area of APOE and we found that right downstream from APOE is another gene which is called APOCI. And we found that there is an area of APOCI that is also linked with the disease."

Now researchers need to narrow down that area and identify the gene and what it does, which should be easier with the aid of the sequencing done for the Human Genome Project, Dr. Poduslo said.

"I have a feeling we're looking for a gene that's never been identified," she said.

Dr. Poduslo's work is driven by the assistance of families - she has banked more than 10,000 samples from 2,400 families.

The work bore fruit with 14 large extended families with several siblings. In addition to the work on chromosome 19, she has also identified areas on chromosome 12 and chromosome 3 which were linked to the disease in different extended families.

The work might help explain what researchers have long suspected, that the disease takes different courses and different forms and is likely the work of multiple genes, said MCG Alzheimer's researcher William David Hill.

"It's probably multiple genes, not just single genes, which are putting people at risk, and it's going to be very difficult teasing apart the different combinations that may need to come together to cause the disease," Dr. Hill said. "Sometimes you have genes clustered together who function together. So it certainly makes sense that on chromosome 19 that more than APOE may be involved. How it is tied into APOE is a mystery at this point."

Dr. Poduslo would like to take that connection one step further by tying it to the course of the disease.

"We know that some (patients) have problems with language, some wander, some have outbursts of anger, some seem depressed," Dr. Poduslo said. "What we'd like to do is try to correlate some of these clinical findings with the mutated gene. And see, well, if this person has this mutated gene, he may likely go down this road and have these symptoms with Alzheimer's."

That correlation could be taken further by testing different drugs against the different mutations to determine which drug would be most effective with each. This might one day allow doctors to tailor medications to a patient's particular genetic cause, Dr. Poduslo said.

"We need to identify what genes are there," she said. "We need to be able to identify patients early, before all this damage in the brain is done and we need to find a way of treating this so the damage does not occur."

And she needs more families to help.

TO PARTICIPATE

If you are a family affected by Alzheimer's disease and would like more information on the DNA bank at the Medical College of Georgia, call (706) 721-0609 or (866) 207-1267. More information also can be found at www.mcg.edu/alzres.

Reach Tom Corwin at (706) 823-3213 or tomc@augustachronicle.com.