Another Risk Factor for Alzheimer's?

Continued from page 1

By Jennifer Chu

Tuesday, January 16, 2007

After analyzing 29 areas along the SORL1 gene that may harbor variations, normal or otherwise, scientists found two specific locations where variations were particularly present in those with late-onset Alzheimer's. They hypothesize that these variations may be suppressing SORL1's normal ability to steer app away from the forbidden zone.

"One of the reasons we're encouraged by our findings is that we have observed the association in a large number of data sets," says Farrer. "When you see it coming up again and again, we all get more heartened."

Farrer's next step is determining exactly how much of a risk these genetic variations pose for developing Alzheimer's. Identifying genetic risk factors could help in early detection and treatment of the disease. To date, only one gene, apoe-4, has been singled out as a genetic risk factor for Alzheimer's. People who inherit one copy of apoe-4 have an increased risk of developing the disease, while people who inherit two copies have an even higher risk, although the presence of apoe-4 does not guarantee that the disease will manifest.

Rudolph Tanzi, professor of neurology at Massachusetts General Hospital, recently coauthored a meta-analysis with Harvard colleague Lars Bertram comparing every study in the scientific literature having to do with genetics and Alzheimer's. Their results confirmed that apoe-4 is the strongest known risk factor. As for other possible genes, he found that most that have been associated with Alzheimer's tend to have much smaller effects, including Farrer's recently studied SORL1.

"If apoe-4 is a major leaguer, these [other genes] would be in the minor leagues," says Tanzi.

Still, many researchers believe Alzheimer's disease may be caused by a complex interaction of these minor-league genes. People who have one kind of gene may develop Alzheimer's, while others with the same risk gene may not, based on the presence of other genes that might protect against the disease.

"None of these genes are in a vacuum," says Farrer. His colleague Steven Younkin, chair of the pharmacology department at the Mayo Clinic in Jacksonville, FL, echoes the need to identify genetic markers.

"It's always hard to know which avenue is going to prove more fruitful," says Younkin. "We need a diverse portfolio to influence this disease."