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Alzheimer’s Yields New Genetic Clues

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By The New York Times and The Washington Post

Two teams of European scientists say they have discovered new genetic variants associated with Alzheimer’s disease. The variants account for about 20 percent of the genetic risk of the disease and may lead to a better understanding of its biology, the scientists say.

At least 5 million Americans have Alzheimer’s disease. By one estimate, one in seven people age 72 and older has dementia, with Alzheimer’s the most common form.

The new findings, reported Sunday in the journal Nature Genetics, will have no immediate consequence in either diagnosis or treatment, but will help illuminate a process that goes on for years or even decades before memory loss becomes apparent.

Statistically significant

One of the teams, led by Julie Williams of Cardiff University in Wales, scanned the genomes of about 19,000 patients, the largest study so far conducted on Alzheimer’s, and turned up two variants that have a statistically significant association with the disease.

A second study, led by Philippe Amouyel of the University of Lille in France, also found two variants, one of which is the same as detected in Cardiff.

The fact that two studies could agree on at least one gene is an advance. More than 550 genes have been proposed in various small-scale studies as the cause of Alzheimer’s, but all have failed the test of replication by others, Amouyel said.

“The message here is that genes are important in Alzheimer’s disease … and there may be multiple ways of reducing the risk that the genes produce,” said Williams, a neuroscientist.

All “Alzheimer genes” have normal roles in brain physiology; they don’t exist solely to cause dementia. Instead, small variations in their DNA alter their function and, through processes only now being uncovered, increase or reduce the risk of developing the disease.

Two of the genes described in the new research may be involved in determining the brain’s capacity to clear itself of toxic “amyloid” proteins that collect outside neurons, eventually poisoning them.

The most important previously known Alzheimer gene promoted overproduction of amyloid. The new findings suggest that at least two processes – production of amyloid and its removal – are involved in the disease.

The genes were found through “genome-wide association studies,” in which long stretches of DNA are examined for small differences between individuals.

With the advent of cheap, fast DNA sequencing, the studies have become a powerful way to uncover genes that make small contributions – along with environmental influences and personal choice – to a person’s overall risk for such chronic ailments as diabetes, coronary heart disease and depression.

Big factor

Neuroscientists believe 60 to 80 percent of a person’s risk of developing Alzheimer’s disease is attributable to genes. Knowing which they are and what they do may provide targets for drugs and other interventions.

“Hopefully they will point us to parts of a physiological pathway where we can do some tweaking,” said Stephen Snyder, deputy director of the National Institute on Aging, who was not involved in the studies.

Some studies of people with arthritis have found that those taking anti-inflammatory drugs for long periods may have lower rates of Alzheimer’s.

“Fighting against inflammation may be a clue to fighting against Alzheimer’s,” Amouyel said, noting it’s just speculation now.

Copyright © The Seattle Times Company

original link:  http://seattletimes.nwsource.com/html/health/2009818715_alzheimers07.html?syndication=rss