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Mon August 25, 2014

People With Down Syndrome Are Pioneers In Alzheimer's Research

Originally published on Tue August 26, 2014 7:53 am

When researchers at the University of California, San Diego wanted to study an experimental Alzheimer's drug last year, they sought help from an unlikely group: people with Down syndrome.

"I had a CAT scan on my head, and I was in a special machine. It's called an MRI," says Justin McCowan, 39, whose parents drove him 125 miles from Santa Monica so he could participate in the study. McCowan also took brain function tests and spent hours with a needle in his arm so researchers could monitor levels of certain chemicals in his blood.

Alzheimer's researchers are increasingly interested in people like McCowan because "people with Down syndrome represent the world's largest population of individuals predisposed to getting Alzheimer's disease," says Michael Rafii, director of the Memory Disorders Clinic at UCSD.

Down syndrome is a genetic disorder that's best known for causing intellectual disability. But it also causes Alzheimer's. "By the age of 40, 100 percent of all individuals with Down syndrome have the pathology of Alzheimer's in their brain," Rafii says.

Down syndrome is caused by the presence of an extra copy of chromosome 21. And one of the genes on chromosome 21 happens to control the production of amyloid, the substance that forms the sticky plaques associated with Alzheimer's.

Because their bodies produce extra amyloid, most people with Down syndrome develop problems with thinking and memory by the time they reach 60. Rafii has chronicled the decline of one of his patients, a woman named Irma, by collecting her signatures from medical forms over the years.

The first one is from 1999, when Irma was in her mid-50s. "You can see her signature is on the line, it's clear, she wrote it in script," Rafii says. By 2005, though, she has switched to large block letters. By 2009, Irma is misspelling her name. By 2011, "there are only a few characters written that resemble letters," Rafii says. "And in the very last year it's completely blank."

People like Irma used to be rare because the medical problems associated with Down syndrome meant they rarely lived long enough to get dementia. Today, though, better medical treatments mean people with the disorder often live into their 60s.

And that has created a huge opportunity for Alzheimer's research, says William Mobley, chairman of the neuroscience department at UCSD. "This is the one group in the world that you could argue would benefit most by the institution of early therapy," he says.

Early therapy means starting people on drug treatment years before the symptoms of Alzheimer's appear. The approach has been hard to test because, in the general population, there's no good way to know who is going to develop Alzheimer's. But for people with Down syndrome, it's a near certainty.

Finding a drug that prevents Alzheimer's in people with Down syndrome could help millions of people who don't have the disorder, Mobley says. "This approach to treating Alzheimer's disease might apply to all of us," he says. "Imagine someday a drug that we all start taking when we're 25 so we never get Alzheimer's disease."

That's a long-term goal. But already, people with Down syndrome are making a difference in Alzheimer's research. Early work with Down patients helped confirm the importance of amyloid. More recently, people with the disorder helped test an eye exam that may offer a simple way to screen for Alzheimer's.

And then there's the study that Justin McCowan signed up for. It involves a drug from Transition Therapeutics called ELND005 that, in mice, can prevent the brain changes associated with Alzheimer's. Scientists hope the drug can do the same thing in people, including those with Down syndrome.

McCowan says he volunteered for the study because he wants to help other people, especially a friend of his named Maria, who also has Down syndrome. "I feel very sad about Maria because she doesn't remember anything," McCowan says.

His parents, Don and Annamarie McCowan, say their son's memory is still sharp. They hope that what scientists are learning from people like Justin will keep it that way.

Copyright 2014 NPR. To see more, visit http://www.npr.org/.

Transcript

STEVE INSKEEP, HOST:

It's MORNING EDITION from NPR News. I'm Steve Inskeep.

DAVID GREENE, HOST:

And I'm David Greene. Today in Your Health, enticing kids into the produce aisle.

INSKEEP: But first we'll report on the effort to understand Alzheimer's disease. Scientists are getting some clues from an unlikely source - people with Down syndrome are becoming pioneers in Alzheimer's research. NPR's Jon Hamilton explains.

JON HAMILTON, BYLINE: At a clinic in La Jolla, California, a dark-haired man in a T-shirt and sneakers is taking a test.

JUSTIN MCCOWAN: Oh, yeah.

HAMILTON: A researcher named Michelle Herman is making sure he knows what to do.

MICHELLE HERMAN: But she asked you to do some things with these blocks to understand how your brain works, right?

MCCOWAN: Yeah.

HAMILTON: The task is to arrange the blocks in the shape of two red diamonds.

MCCOWAN: Wahl ah.

HAMILTON: Wahl ah?

MCCOWAN: Two red diamonds.

HAMILTON: The man's name is Justin McCowan.

MCCOWAN: Justin Paul Donald McCowan.

HAMILTON: And how old are you Justin?

MCCOWAN: Thirty-nine.

HAMILTON: Justin lives 125 miles way in Santa Monica. His parents have been bringing him this clinic, run by the University of California San Diego, because he has an unusual brain.

MCCOWAN: Yes, I do have down syndrome.

HAMILTON: Down syndrome is a genetic disorder that's best known for causing intellectual disability. But Michael Rafii, who's in charge of the clinic, says the disorder also causes another problem.

MICHAEL RAFII: People with Down syndrome represent the world's largest population of individuals predisposed to getting Alzheimer's disease.

HAMILTON: That's because Down syndrome is caused by the presence of an extra copy of chromosome 21. One of the genes on chromosome 21 happens to control the production of something called amyloid. And amyloid is what forms the sticky plaques associated with Alzheimer's. Rafii says in people with Down syndrome, these amyloid plaques start to appear in childhood.

RAFII: By the age of 40, 100 percent of all individuals with Down syndrome have the pathology of Alzheimer's in their brain.

HAMILTON: And most go on to develop problems with thinking and memory by the time they reach 60. Rafii tells me about one of his patients, a woman named Irma. He shows me a medical form that Irma signed in 1999 when she was in her mid-50s.

RAFII: You can see her signature is on the line, it's clear, she wrote it in script.

HAMILTON: Then Rafii shows me more signatures from Irma. Five years after the first one, her script has become larger and less precise. In the sixth year, she abandons cursive for large, block letters.

RAFII: About 10 years into it, she's really misspelling her name. And by the last year, there are only a few characters written that resemble letters. And in the very last year, it's completely blank.

HAMILTON: People like Irma used to be rare because the medical problems associated with Down syndrome meant they usually didn't live long enough to get dementia. Today, though, people with the disorder often live into their 60s. And Bill Mobley, who chairs the Department of Neurosciences at U.C. San Diego, says that has created a huge opportunity for Alzheimer's research.

BILL MOBLEY: This is the one group in the world that you could argue would benefit most by the institution of early therapy.

HAMILTON: Early therapy means starting people on drug treatment years before the symptoms of Alzheimer's appear. It's still not clear whether it works. And it's been hard to test because in the general population, there's no good way to know who is going to develop Alzheimer's. But for people with Down syndrome it's a near certainty. And, Mobley says, finding a drug that works for them could help millions of other people.

MOBLEY: This approach to treating Alzheimer's disease might apply to all of us. I mean, imagine someday a drug that we all start taking when we're 25 so we never get Alzheimer's disease.

HAMILTON: That's a long-term goal. But already people with Down syndrome are making a difference in Alzheimer's research. Early work with Down patients helped confirm the importance of amyloid. More recently, people with the disorder helped test an eye exam that may offer a simple way to screen for Alzheimer's. And then there's the study that Justin McCowan signed up for.

MCCOWAN: I had a CAT scan, and I was in a special machine. It's called an MRI.

HAMILTON: The study is testing a drug known to prevent Alzheimer's in mice. To help gauge it's effect in people, Justin spent hours with a needle in his arm while researchers monitored levels of certain chemicals in his blood. He says he volunteered for the study because he wants to help people, especially a friend of his who also has Down syndrome.

MCCOWAN: Her name is Maria. And I feel very sad about Maria because she doesn't remember anything.

HAMILTON: Justin's parents, Don and Annamarie McCowan, say their son's memory is still sharp. They hope that what scientists are learning from people like Justin will keep it that way. John Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.