Scientists in France and Wales have discovered three genetic markers that convey a higher risk of developing late-onset Alzheimer’s disease. However, the increased risk revealed by those DNA variations is not nearly as potent as that tied to another marker, called APOE, which has been used since 1993 to predict a patient’s proclivity for developing the disease.

Researchers believe that 60 to 70 percent of Alzheimer’s disease cases are inherited, with about 20 to 25 percent caused by the previously identified gene variation. The newly associated genes include CLU, which is estimated to be responsible for about 9 percent of Alzheimer’s cases, and CR1, which is thought to account for about 4 percent of cases.

Testing positive for the new genetic variations increases a carrier’s risk of disease by up to 20 percent–much less than the 50 to 100 percent increase produced by the APOE marker.

In two studies, published this week in the journal Nature Genetics, populations of thousands of Europeans–some with and some without Alzheimer’s–were scanned for genetic mutations that might be associated with the disease. This type of genome-wide association study involves testing hundreds of thousands of DNA markers and using sophisticated statistical methods to pluck out those that seem to be predictive in people who carry an inherited disease. This type of study can also provide clues as to what role the genes play in causing or preventing maladies.

The responsibility of the CLU and CR1 genes in the onset of Alzheimer’s disease is not yet known, says Philippe Amouyel, an epidemiologist at the University of Lille in France and an author of one of the studies. “But previous studies suggest that they may be involved in the elimination of the major component of amyloid plaques.” Buildup of these plaques is a major cause of Alzheimer’s.

A third genetic marker, in the PICALM gene, also may contribute to the clearance of amyloid plaques, according to Julie Williams, professor of neuropsychological genetics at Cardiff University in Wales.

“This combination of discoveries forms an important breakthrough in the current impetus to discover the causes of Alzheimer’s disease,” Williams says. She adds that CLU, CR1, and APOE all seem to have roles in protecting the brain from damage. “Perhaps the changes we see in these genes remove this protection or may even turn them into killers,” she says.