June 26, 2008

Researchers Identify Gene Linked to Alzheimer’s

A gene that raises the risk of Alzheimer's disease by at least 45 percent, and possibly higher, has been identified by New York scientists and an international team of gene hunters.

The discovery helps add context to what any layperson can see but what scientists have yet to fully explain: Most cases of Alzheimer's occur in people who are 65 and older. Until now, only one gene had been identified as a likely culprit _ ApoE4.

Now, Philippe Marambaud of the Feinstein Institute for Medical Research in Manhasset, and Fabien Compagne at Weill Medical College of Cornell University in Manhattan, have found another. They've dubbed the newly isolated gene CALHM1.

"What we found is that risk is completely independent from ApoE4, but it is possible for someone to be affected by both," Marambaud said of a double whammy inheritance pattern that could dramatically increase chances of Alzheimer's disease.

"But what I want to emphasize is that there is no cross-talk between these two genes," he said of the pair's inability to act in concert. Each when mutated possesses the capacity to confer Alzheimer's by itself.

The National Institute on Aging calls Alzheimer's a major public health concern that will only worsen unless steps are taken now to understand its myriad causes. Experts predict an explosion of cases in coming years as baby boomers age.

Currently, 4 million people in the U.S. have Alzheimer's, which doctors describe as progressive and irreversible, characterized by a decline in cognitive, behavioral and physical abilities.

Several genes have been found that confer risk for so-called early-onset Alzheimer's. Marambaud and Compagne were on a search for a gene that steals a lifetime's worth of memories in old age.

"Early-onset disease, which can begin as early as 30, is very rare," said Marambaud, who was aided by researchers elsewhere in the United States and abroad. "The vast majority of cases are late-onset disease."

He and Compagne, who report their results Friday in the journal Cell, began the hunt for variant DNA in the brain's hippocampus, which serves as the organ's memory control center. Anything gone seriously awry here might be a tipoff to the underlying biology of the disease, the scientists hypothesized.

In a study involving tissue samples from 2,000 people with Alzheimer's and 1,400 without it, they made a startling discovery about calcium, vital to the function of all cells, especially those in the brain.

Calcium enters cells through special channels. Once inside, calcium helps relay critical signals. But when CALHM1 is present, less calcium gets in, weakening cell signaling, the chemical process of human thought.

Doctors not connected with the research commended it for its enterprising look at calcium. A yet-to-be-designed drug that acts on calcium channels could help preserve the minds of those affected by CALHM1-mediated Alzheimer's disease, they said.


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