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Secrets to Alzheimer's sought in link to Down syndrome

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By Bloomberg News
Sunday, Nov. 17, 2013, 6:00 p.m.

Research to unravel for the first time the complex genetic mechanisms shared by Alzheimer's disease and Down syndrome is gaining momentum in studies by Johnson & Johnson and patient advocacy groups.

By 40, almost everyone with Down syndrome has beta amyloid deposits in their brains reflective of the protein clumps seen in Alzheimer's in the general population, autopsy and imaging studies show. By 50, half have dementia.

While the high incidence in Down patients has been noted for decades, scientists are only now seeking to use the quicker progression to gauge how Alzheimer's grows in the general population.

At a time when drug companies have been frustrated in their efforts to slow the disease, the link to Down syndrome may hold the promise of a new path toward finding an effective treatment.

“In a way, Down syndrome is a model disease for Alzheimer's,” said Mike Krams, vice president of quantitative sciences at J&J's Janssen Pharmaceuticals unit, which met to discuss a three-year pilot study.

Not everyone with Down syndrome shows signs of dementia as they age, even as the amyloid accumulates. Finding out what prevents Alzheimer's in these patients may provide clues for the general population, Krams said.

The New Brunswick, N.J.-based company is developing a drug meant to stop or slow beta amyloid formation by preventing a parent protein from being cut into smaller parts. Because Down syndrome patients have extra amounts of this precursor protein, they may benefit from that drug, Krams said.

At the same time, five researchers in the United States and Israel last month were awarded a combined $1.2 million to investigate aspects of the link between the diseases in an effort bankrolled by the Global Down Syndrome Foundation in Denver and the Chicago-based Alzheimer's Association.

Studies into Down syndrome have long presented challenges and are often blocked by family members or legal guardians. Now, by using improved genetic data, new scanning technology and better cognitive testing, researchers in both diseases are able to gather data in a bid to track Alzheimer's progress in living patients, rather than having to wait to perform autopsies.

“Most people who study Alzheimer's disease don't really see individuals with Down syndrome frequently,” said Ira Lott, head of the University of California at Irvine's Down syndrome program. “It's been a matter of cross-communication.”

The grant to the five researchers was awarded Oct. 29, and it's designed to support work that is investigating the interplay of certain genes that may lead to overproduction of beta amyloid; whether certain biomarkers can be used to track disease progression in Down syndrome patients; and whether it's possible to make a DNA vaccine.

Researchers will start their work as life expectancy of those with Down syndrome has doubled to 60 during the last 30 years, according to the National Institutes of Health.

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