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Chromosome 21?: UCI researchers studying link between Down syndrome and Alzheimer’s

June 13, 2016


IRVINE, Calif. — When Ruth Russi was born with Down syndrome in 1959, her parents were told she would die before her fifth birthday. By the time Ruth turned 50, John and June Russi of Costa Mesa, Calif., began to prepare for her outliving them.

But as she aged, Ruth’s behavior changed. She would stare at her crayons, unable to color, or walk out of church still clutching a dollar bill for the offering.

John, 85, and June, 79, were devastated to learn that Alzheimer’s disease, a condition they worried about for themselves, had inhabited their daughter’s brain. Ruth died last fall, a week before her 56th birthday.

"We’d always been able to make her happy one way or another," John Russi said. "At the end we couldn’t make her happy. That hurt."

Those with Down syndrome are not only more susceptible to Alzheimer’s, but they experience onset at younger ages. Longer lifespans are creating caregiving burdens for families like the Russis and driving more research into the genetic connection between the developmental disorder and degenerative brain disease.

UC Irvine has received $4.7 million from the National Institute on Aging to launch a five-year study this summer aimed at identifying who with Down syndrome is most at risk for developing dementia.

"I think the urgency in part reflects the urgency of Alzheimer’s research," said Dr. Ira Lott, a pediatric neurologist and lead researcher. "Alzheimer’s is a tremendous national problem. Many people with Down syndrome live productive and happy lives. To have that cut off prematurely by Alzheimer’s disease is a tragedy that we’re trying to prevent."

The findings could result in better treatment options and yield discoveries that would also benefit the general population.

"Anytime we can shine a light on any aspect of this disease, that is massively important," said Jim McAleer, CEO of Alzheimer’s Orange County. "It’s vitally important for those people and their families that we learn how to treat this disease and cure it in that population. Science might learn more about the disease because of the genetic difference in that population. I think it actually can move science forward."

EXTRA GENES

People with Down syndrome are born with an extra copy of chromosome 21, which causes intellectual disability and a distinct facial appearance. Chromosome 21 also carries a gene that produces a protein that forms the plaques in the brain that increase the risk of Alzheimer’s.

The triplication of the chromosome appears to prime the brain for Alzheimer’s, with autopsies showing that most people with Down syndrome have the neuropathological indicators of the disease by age 40.

But despite those structural changes, not everyone exhibits symptoms.

"Why do some with Down syndrome become demented and some don’t?" Lott said of his research focus. "We think this is not only important for Down syndrome but for understanding Alzheimer’s disease."

Lott hopes to discover what biomarkers predict who will develop dementia so treatment can be introduced early, particularly as new therapies become available. He’s recruiting 100 volunteers with Down syndrome, over age 40, to undergo cognitive and memory tests, brain scans, blood work and testing of spinal fluid.

"Because of the biology of Down syndrome, there’s a special window here for understanding the process of Alzheimer’s disease," Lott said.

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VOLUNTEERING

Gerard Fobes, 45, of Newport Beach, Calif., plans to volunteer for Lott’s study after losing two childhood friends to Alzheimer’s as well as his maternal grandmother. He doesn’t mind giving blood or remaining still in a confined imaging machine.

"I just like being a part of it," he said. "I do know my Grandma had dementia. A lot of European elderly have it."

His mom, Jeanne Fobes, responded, "That’s why you’re doing it, Gerard. You gotta get a cure for us before we get it."

Fobes, who works every Saturday at Ralphs, starred in Garth Brooks’ 1993 music video "Standing Outside the Fire." He loves researching academic topics on his computer and volunteering with his dad at a local food bank.

Jeanne Fobes, 84, said she believes her son will be particularly useful to researchers because of his intelligence.

"There’s a whole lot of intriguing stuff going on with Gerard," she said. "He remembers everything he has researched. He’s just very bright."

Lott, who has worked with Fobes in past Down syndrome research projects, said it’s unknown whether high intelligence could lend some protection against Alzheimer’s.

"It’s better, I think overall, to be on the higher functioning side because you probably have a bit more of a brain reserve," he said.

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DIAGNOSIS

For adults with Down syndrome, the earliest signs of Alzheimer’s may look different because their intellectual disability can at times mask memory loss. They may experience behavior or mood changes, as well as difficulty walking.

"Commonly they have a personality change," Lott said. "People with Down syndrome are typically very outgoing and socially motivated. They lose this interest. They also develop problems with their memory, which are pretty similar to Alzheimer’s in the general population."

Some patients express frustration that they can’t think as well as they used to. They also often become very depressed after a friend or roommate dies of Alzheimer’s.

"They understand the loss but they don’t really understand the process," Lott said of the disease.

Lott said Alzheimer’s puts a tremendous burden on parents who are often older to begin with because the prevalence of Down syndrome is higher for children whose mothers give birth after 35.

For Ruth, the oldest of three, Alzheimer’s eventually stole her cheerful disposition and enjoyment of the simple pleasures in life. Her favorite place was Disneyland, where she would ask to ride It’s a Small World over and over again.

"The things she liked made her really happy and joyous," John Russi recalled. "You don’t see it in a normal person. Nobody smiles all the time and she did."

But as her illness progressed she lost her limited vocabulary, even her favorite word, bird. She could no longer live in her group home and moved to a long-term care facility. She stopped erupting in excitement when she saw her parents and would ignore them when they visited.

After she died, her parents donated her brain to UCI.

"Dr. Lott said her brain will be used for years to come," June Russi said. "We wanted to help research. She didn’t need it anymore."

To learn more about the UCI Down Syndrome Program please contact Eric Doran at 714-456-8443 or edoran@uci.edu

 

 


Associated Press