Path of Alzheimer's disease risk gene tracked, scientists say

Scientists have mapped the step-by-step actions that lead to late-onset Alzheimer's disease, research that may offer new paths to developing treatment.

People who carry the APOE4 gene, known to increase the risk of acquiring Alzheimer's later in life, experienced changes in the expression of genes in their brains that resembled those of Alzheimer's patients, a study published yesterday in the journal Nature reports.

The changes in gene expression may point to early markers of the disease, and may help develop drugs for Alzheimer's, for which there is so far no treatment or cure. They also bolster the idea that Alzheimer's disease alters the brain long before patients become forgetful, said Dean Hartley, the director of scientific initiatives for the Alzheimer's Association, an advocacy organization in Chicago. He wasn't involved in the study.

"We do need to understand more about the mechanisms involved in Alzheimer's disease's initiation and progression," Hartley said, noting there haven't been any successful clinical trials for drugs that try to alter the disease's path. "This paper . . . may suggest targets or pathways to look for new drugs."

The research also suggests that doctors should look to treat patients before they become forgetful, Hartley said. Studies like this one may help identify places to intervene before symptoms appear, he said.

More than 5 million people in the United States have Alzheimer's, the most common form of dementia, and the number may increase to as many as 16 million by 2050, according to the Alzheimer's Association.

There has been growing interest among scientists in what happens in the brain before a patient is diagnosed with clinical Alzheimer's. The new study is meant to help understand those changes at the molecular and cellular levels, said Asa Abeliovich, a study author and neuroscientist at Columbia University.

The APOE4 gene increases the risk of developing late-onset Alzheimer's by three times in those who have one copy of the gene, and 10 times in those who have two. While APOE4, first identified in 1991, raises the risk of getting Alzheimer's, most people with the mutation don't develop dementia, Abeliovich said. That suggests some other factor may be required for Alzheimer's to begin. The most important non-genetic risk factor for Alzheimer's is age.