Researchers have found five new genes that are linked to a person's risk for Alzheimer's disease.

Each of the genes may make a person 1.1 times more likely to develop Alzheimer's compared with the general population, the researchers say. (Together the five genes would increase that risk by 1.6 times.)

The findings, which come from two new studies that analyzed the genomes of more than 54,000 people, bring the total number of genes known to increase the risk of Alzheimer's to 10.

A gene identified 15 years ago called APOE-e4 has the largest impact on a person's risk of developing Alzheimer's. A person with two copies of this gene (one from each parent) has about a tenfold greater risk of developing Alzheimer's compared with someone without this gene. The other nine genes added together present an almost equal risk, but it would be rare that one person possessed all nine, said Gerard Schellenberg, of the University of Pennsylvania School of Medicine, who led one of the studies.

The researchers now want to learn how these genes contribute to Alzheimer's.

"We have new genes that tell us there are brand-new pathways that we have to now consider as being a part of Alzheimer's that we didn't know before," Schellenberg said. "In the drive to develop some kind of treatment, the more we know and the more different avenues we have to approach, the better chance that we have of finding something that will respond to a drug."

The studies are published in the April issue of the journal Nature Genetics.

Genes and Alzheimer's

Schellenberg and his colleagues from 44 universities and research institutions in the United States first examined the genomes of more than 8,000 individuals with Alzheimer's and more than 7,000 people without Alzheimer's, looking for genetic differences between the groups. They then validated their results in a second group of about 3,500 Alzheimer's patients and 3,500 controls, and a third group of 7,000 Alzheimer's patients and 24,000 controls.

The new genes identified are called MS4A, CD2AP, CD33 and EPHA1.

The second study, which involved researchers from United States, the United Kingdom, France and other European countries, identified the same four genes, confirming the findings, and also found a fifth gene linked to Alzheimer's.

Some of the newly identified genes, as well as APOE-e4, are involved in the transport of fats in the body, Schellenberg said. The researchers hope finding genes associated with the disease will provide clues as to how it arises and first causes problems in the brain. The genes identified were not ones researchers would have expected to be involved in the disease process, Schellenberg said.

Assessing risk

The findings "[add] weight to the idea that the genetics of Alzheimer's disease is complicated," said William Thies, chief medical and scientific officer at the Alzheimer's Association, who was not involved in either study. "We're probably going to have quite a number of genes that have a subtle effect on your risk of developing Alzheimer's disease."

Knowing who's at risk for Alzheimer's will be important once researchers have ways to prevent it , the researchers say.

In addition, once people have an idea of their chance of developing Alzheimer's, they can decide whether the benefits of taking a drug to prevent the disease would outweigh the risks, Thies said.

Pass it on: Four new genes associated with Alzheimer's disease have been identified.

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