Inflammation Gene Defect Linked to Alzheimer’s in Study

A newly discovered gene variant may point to another route Alzheimer’s disease takes to ravage the brain: through the immune system.

The variant, found in less than 1 percent of the population, almost triples the odds of Alzheimer’s disease among its carriers, according to papers published in the New England Journal of Medicine. The findings may provide clues to how the aging brain functions.

The gene helps regulate inflammation, the process by which the body protects itself from invaders. The results released yesterday are encouraging for researchers targeting the immune system as playing a role in the mind-wasting disease, said Norman Relkin, the director of the Memory Disorders Program and a neurologist at New York Presbyterian/Weill Cornell Medical Center. Relkin leads a group testing Baxter International Inc. (BAX)’s Gammagard, an immune system therapy that contains antibodies from healthy people, in Alzheimer’s patients.

“This is a strong supportive line of evidence that inflammation in the immune system plays a role, and for those of us who do clinical trials, especially those with the immune system, it’s encouraging,” Relkin said in a telephone interview. He wasn’t involved in yesterday’s study.

More than 5 million Americans have Alzheimer’s, which is the most-common type of dementia, according to the Alzheimer’s Association. Global dementia cases are expected to double within 20 years to as many as 65.7 million people, the Geneva-based World Health Organization said in April.

TREM2 Gene

In the study, researchers from DeCode Genetics analyzed 2,261 Icelanders and found those with a variant, or defect, on a gene called TREM2 had almost a three times higher likelihood of Alzheimer’s disease than those without the mutation. The scientists also tested a combined 2,000 people in four other groups from the U.S. and Europe, finding similar results.

The researchers determined that carriers of the mutation who were at least 80 years old and without Alzheimer’s disease had poorer cognitive function than their unmutated peers. In July, a DeCode group discovered a mutation that seemed to protect the brain from Alzheimer’s disease. The two findings in combination suggest that the brain ages, said Kari Stefansson, the chief executive officer of Reykjavik, Iceland-based DeCode, and an author of yesterday’s study, in a telephone interview.

“Both these findings support the notion that Alzheimer’s is an extreme form of normal cognitive decline,” Stefansson said. “If you take your skin, your heart, your kidneys, they all undergo evolution as you grow older and your brain is no different. If the deterioration and loss in the capacity of the brain happens in an accelerated fashion, it’s a disease.”

Inflammation Targeted

A second study, led by John Hardy of the University College London Institute of Neurology and Andrew Singleton at the Bethesda, Maryland-based National Institute on Aging, also concluded that a TREM2 variant may play a role. The research found that Alzheimer’s patients were more likely than healthy people to have variants on the TREM2 gene.

Researchers have theorized that inflammation plays a role in Alzheimer’s, and some trials have shown that use of non- steroidal anti-inflammatory drugs, such as aspirin and ibuprofen, decrease the likelihood of the ailment. The studies haven’t been conclusive. Most drugs developed to try to combat the disease have focused on another hallmark, the clumps in the brain of an abnormal form of amyloid protein.

The trial of Baxter’s Gammagard conducted by Relkin will be completed this year, with results to be released in early 2013. Baxter, based in Deerfield, Illinois, doesn’t hold a patent on the drug, also known as IVIG. The treatment has been used for three decades in patients who don’t make enough antibodies to prevent infections.

Though the genetic effect found in yesterday’s research is small, further investigation may lead to drug development, said Gerard Schellenberg, a pathologist at the University of Pennsylvania in Philadelphia, who wasn’t involved in the studies.

“Even if the genetic effect is small, that there’s some risk associated with this gene makes it a valid target,” Schellenberg said.

To contact the reporter on this story: Elizabeth Lopatto in San Francisco at elopatto@bloomberg.net.

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net.

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