Five New Alzheimer’s Genes Double Total in New Push for Cure

Five new genes have been definitively linked to Alzheimer’s disease, doubling the total confirmed by scientists and opening new areas for research into an illness that affects 35 million people globally.

The genetic pathways were reported in two studies involving more than 50,000 people worldwide. Some of the connections found involve systems that control inflammation and cholesterol in the brain, while others affect how brain cells remove toxic proteins, the researchers wrote in reports published yesterday in the journal Nature Genetics.

The newest confirmed genes raise risks for Alzheimer’s by 15 percent or less, not strong enough to be used as a marker for the disease, researchers said. Their worth is in suggesting new areas of study that may one day help speed creation of therapies for a malady that progressively destroys brain cells and makes it difficult for people to think, remember and function.

“We are beginning to piece together the jigsaw and gain new understanding,” said lead researcher Julie Williams, a professor from Cardiff University’s Centre for Neuropsychiatric Genetics and Genomics in Wales. “We still have a long way to go, but the jigsaw is beginning to come together.”

Inflammation, cholesterol and the build-up of beta amyloid protein have long been thought to play a critical role in the degradation of nerve cells in the brain, the researchers said. If treatments can prevent the detrimental effects of the genes, doctors may be able to one day reduce the number of people with Alzheimer’s disease, Williams said.

Important Combinations

Researchers are trying to determine which gene variations, and which combinations, are most important. Identifying how genes work together may speed studies of experimental drugs, said David Bennett, director of the Alzheimer’s Disease Center at Rush University Medical Center in Chicago, in a statement.

“These findings add key information needed to understand the causes of Alzheimer’s disease and should help in discovering approaches to its treatment and prevention,” Bennett said.

The U.S. National Institute on Aging helped fund the studies, which used information gleaned from five different groups, including the Rush Religious Orders Study, to analyze the genetic makeup of more than 54,000 people.

Alzheimer’s is characterized by the formation of plaque in the brain from amyloid and tau proteins. Scientists don’t know why the proteins accumulate or become twisted, whether they cause the illness or if they are an end-product resulting from a different process altogether.

“We know from our studies there are going to be dozens of these genes that will be significant when the collective data is analyzed,” said Rudolph Tanzi, professor of neurology at Harvard Medical School in Boston, and an author of one paper.

Most Exciting

While the combined genes point at several pathways that may play a role in Alzheimer’s disease, Tanzi says he is most excited about CD33, a gene he discovered that is tied to the brain’s primitive innate immune system. In some cases, it might not be eliminating as much beta amyloid as it should. In others, it may be too active and trigger inflammation, he said in a telephone interview.

“Once we figure out what’s going on, CD33 will be a good target because it sits on the cell surface,” he said. “But it will be at least 10 years before we could turn these targets into drugs,” said Tanzi, who is also director of the genetics and aging research unit at Massachusetts General Hospital’s Institute for Neurodegenerative disease.

The number of Alzheimer’s sufferers is predicted to reach 115.4 million by 2050, according to a 2009 report from Alzheimer’s Disease International.

Inevitable Deterioration

No treatment is yet available to slow or stop deterioration of the brain in patients with Alzheimer’s. Drugs aiming to slow the symptoms include Namenda from New York-based Forest Laboratories Inc., and Aricept from New York-based Pfizer Inc. and Tokyo-based Eisai Co.

As much as 80 percent of a person’s chance of developing Alzheimer’s is inherited, doctors say. About 400 genes have been identified that scientists believe may play a role in the condition, named for the German doctor Alois Alzheimer who described it in 1906.

The greatest inherited risk comes from the APOE gene, discovered in 1993 by a team led by Allen Roses, now director of the Deane Drug Discovery Institute at Duke University Medical Center in Durham, North Carolina. A person who inherits that gene from one parent has a 400 percent increased risk of getting the disease.

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