People with Down syndrome may provide key information about genetics of aging

From USA Today:

In 1950, when Marybeth Solinski (pictured) was born, a diagnosis of Down syndrome was practically a death sentence.

Yet Solinski, at 59, has outlived her parents. She has even joined AARP.

Her longevity illustrates the dramatic progress for people with Down syndrome. Thanks to better medical care, the average life expectancy for a child with Down syndrome is now 60 years, according to the National Down Syndrome Society, which estimates that about 400,000 people are living with the condition in the USA.

As they live longer, adults with Down syndrome — who have an extra copy of chromosome 21 — are teaching scientists about the genetic roots of aging, says Ira Lott, head of pediatric neurology at the University of California-Irvine School of Medicine.

Scientists today are searching this chromosome, which contains only about 200 of the body's roughly 20,000 genes, to learn why people with Down syndrome suffer disproportionately from some health problems, such as Alzheimer's disease, but are spared many others, such as heart attacks, strokes and certain types of cancer.

By studying adults with Down syndrome, researchers hope to find new ways to combat diseases of aging in the larger population as well, Lott says.

"It's an interesting detective story," says Lott, head of the science advisory board of the National Down Syndrome Society. "People with Down syndrome are unique when it comes to many aspects of aging."

People with Down syndrome tend to age prematurely as they develop conditions such as menopause, brittle bones, arthritis, hearing loss, wrinkles and sagging skin about two decades earlier than usual, says Brian Chicoine, medical director of the adult Down syndrome center at Advocate Lutheran General Hospital in Park Ridge, Ill., the leading center of its kind.

"People say they seem to age overnight," says Dennis McGuire, director of psychosocial services at the same center. "They suddenly develop wrinkles and gray hair."

Solinski, for example, wears a brace on one leg and hearing aids in both ears, and she has had two corneal transplants. "She's more like a 79-year-old than a 59-year-old," says her sister, Lee Cornell of Illinois.

Yet researchers suspect that this unique genetic profile also protects people with Down syndrome from many common ailments. A growing number of researchers are asking:

•What protects their hearts?

Half of babies with Down syndrome are born with correctable heart defects, and most adults with Down syndrome are overweight with high cholesterol. Despite these risks, however, people with Down syndrome virtually never develop high blood pressure, heart attacks or hardening of the arteries, Lott says. Doctors are still trying to learn why.

•Why don't they get cancer?

Doctors once believed that people with Down syndrome didn't live long enough to develop cancer, says Sandra Ryeom, a researcher at University of Pennsylvania School of Medicine in Philadelphia

Yet, with the exception of a rare pediatric leukemia, even elderly adults with Down syndrome rarely develop solid tumors, such as those of the breast or lung.

Last May, Ryeom and her colleagues found genes on the 21st chromosome that inhibit the growth of blood vessels necessary for tumor growth. Getting an extra copy of these genes, and possibly others, may help the body keep cancers in check by depriving them of blood, she says.

Researchers already are trying to develop anti-cancer treatments based on genes found on chromosome 21, says Roger Reeves of Johns Hopkins University School of Medicine.

•What protects their eyes?

Although people with Down syndrome are at higher risk for cataracts, they rarely develop a form of blindness called macular degeneration, caused by an overgrowth of blood vessels in the retina, Ryeom says. Doctors suspect that the same genes that restrict blood vessel growth in tumors may also prevent abnormal blood vessel growth in the eye.

•Why do Down syndrome patients develop early Alzheimer's disease?

Adults with Down syndrome appear to develop the brain plaques and tangles characteristic of Alzheimer's disease very early in life — even as young as 3 or 4 years old. For decades, however, their brains also appear to repair and compensate for the damage, says scientist Elizabeth Head of the University of Kentucky's Sanders-Brown Center on Aging.

"Their brains may be clearing the plaques," says Head, who is now recruiting Down syndrome patients for a study on biomarkers of Alzheimer's. "As they get older, this protective process slows down."

By age 40 to 45, virtually everyone with Down syndrome has these plaques and tangles, although only 12% have dementia, Lott says. By age 65, up to 75% of people with Down syndrome have dementia.

Significantly, doctors have found a gene that increases the risk of Alzheimer's, called APP, on the 21st chromosome, Lott says. The gene, called amyloid precursor protein, is involved in the creation of the brain plaques seen in Alzheimer's patients. People who inherit mutated copies of these genes may develop Alzheimer's disease decades earlier than usual, says William Mobley, a neuroscience professor at the University of California-San Diego.

Yet not all people with Down syndrome succumb. One of Chicoine's patients lived to 83 without dementia.

Solinski, of Chicago, loves learning so much that she takes flash cards on vacation. She pores over children's encyclopedias and Nancy Drew novels. She is learning to cook, she says, to follow in the footsteps of her mother, who died in August at 92. And, she says, "I want to be a great reader like my father."

And Brooklyn resident Edward Barsky is still healthy and independent at 73, living in a group home and navigating public transportation on his own, says his sister, Vicki Ploscowe.

"He's still going strong," says Ploscowe, of Manhattan.

If researchers could learn what protects certain people, they might be able to develop a therapy to prevent Alzheimer's — both in those with and those without Down syndrome, Head says.

People with Down syndrome present doctors with a rare opportunity to watch the disease progress, Lott says.

"There's no other population where you can really study this," Lott says. Although some people without Down syndrome carry a gene that increases their risk of early dementia, "you don't know who in the general population is going to come down with sporadic Alzheimer's. With Down syndrome, you know that virtually 100% of them will have plaques."

For example, doctors don't yet know exactly how an extra copy of chromosome 21 causes or prevents disease, Lott says. It's possible that getting a 50% larger "dose" of a gene affects the body's susceptibility to a disease, he says. Or, it's possible that the extra genetic material simply makes the entire genome more unstable.

Reeves says he's grateful to the Down syndrome community for teaching scientists so much.

"If it weren't for people with Down syndrome having fewer tumors," Reeves says, "we never would have thought to look for anything like this."