| ||||||
|
|
|
|
|
|
|
|
|
 |
 |
 |
 |
|
 |
She was following behind
when her sister turned the wrong way on the "I started
screaming," McCulley says now about the incident, which took place in
2000. They both got home safely, but McCulley took the car keys from her
sister then and there. "She didn't
understand," McCulley says. "She just thought I was being
mean." Her sister had
Alzheimer's. McCulley, who is now 65, cared for her sister for four years
until she died of the disease at age 86 on Now McCulley, of McCulley's family likely
has inherited a gene or genes that put them at risk of developing
Alzheimer's late in life. Not everyone in the family gets it, but some do:
McCulley's dad probably died of the disease, as did several other close
relatives. McCulley has experienced
no sign of Alzheimer's, but each passing year adds to her risk: "If
I'm going to get this disease it'll be in the next 10 years." Instead of worrying about
the future, McCulley took a step that she hopes might one day push the
clock back on Alzheimer's — if not for her, then for the next
generation: She got her family to participate in a just-completed study of
Alzheimer's, one that identified a gene that might control not just
whether someone gets the disease, but when. That finding, which
appeared in the Dec. 15 issue of Human Molecular Genetics, might one day
lead to powerful new drugs that could slow the disease down — possibly
forever. "If you could delay
the onset of disease past the natural life span — that would be very
powerful," says Margaret Pericak-Vance, the lead researcher on the
study. Seeking genetic clues Late-onset Alzheimer's,
which generally strikes past age 60, is the most common form of the
disease. In the past, researchers had focused on genes that put people at
risk of getting the disease. Pericak-Vance and her colleagues at "Why do some people
get it when they're 60 and others get it when they're 80?" Pericak-Vance
asks. To find out, the team
began to comb through the genetic material isolated from blood donated
from families with a history of Alzheimer's. Last year, the team had
narrowed the search down to a region on chromosome 10, a stretch of DNA
that contained hundreds of genes. Eventually, the team had
whittled the number of candidate genes down to four and then finally homed
in on one, a gene known as GST01, or Gusto for short. Their research suggested
that people who had inherited one version of the Gusto gene might get
Alzheimer's at the earlier end of the age spectrum, for instance in their
60s rather than much later. This study also suggested
that the same gene influenced the age at which people developed another
brain disease, Parkinson's. About 1 million Americans have Parkinson's
disease, a movement disorder that causes tremors and a slow, shuffling
walk. No one knows for sure how
Gusto might influence the timing of either disease, but studies suggest
this gene is involved in regulating the brain's inflammatory response.
Some scientists believe that inflammation plays a role in both diseases. The most common form of
Alzheimer's is probably caused by a mix of genetic and environmental risk
factors. There's no evidence that Gusto triggers the disease itself. But
one version of the gene may accelerate the silent destruction of the brain
so that symptoms start at an earlier age. Genes like Gusto give
human cells the instructions to make a specific protein. The Duke team
believes this version of Gusto may somehow spur the disease on. If it
does, and if researchers can figure out how it works, they might be able
to fashion a drug that blocks the protein — and thus slow the
progression of the disease by several years. And if drug designers got
lucky, they might push back the clock on Alzheimer's even more — from
age 80 to 90 or even 100, says William Scott, a Duke epidemiologist: "That might help
people escape the disease altogether." More therapies needed Researchers know it takes
decades for Alzheimer's to ravage the brain. If a drug could stop the
disease before it destroyed large parts of the human brain, that might
prevent the confusion, memory loss and behavioral problems that are
hallmarks of a disease that now afflicts about 4.5 million people in the Better therapies are
urgently needed for members of the boomer generation, who are rapidly
approaching the high-risk zone for Alzheimer's. The number of Americans
who suffer from Alzheimer's may hit the 16 million mark by the year 2050,
says Bill Thies of the Alzheimer's Association in But first, scientists will
have to prove that the Gusto gene actually does control the age of onset.
Other researchers may find the link between Gusto and Alzheimer's doesn't
hold up. "One paper doesn't mean this finding is buttoned down,"
says Marcelle Morrison-Bogorad, an Alzheimer's expert at the National
Institute on Aging, part of the National Institutes of Health in Bethesda,
Md. Yet many experts think the
Gusto finding will pan out. "My guess is this finding is real,"
says Richard Mayeux, a neurologist and Alzheimer's expert at If it is, and if
additional research goes well, scientists might one day fashion a therapy
that delays the onset of Alzheimer's by 10 years. But even a delay of a
few years would be worth it for many seniors, Mayeux says. McCulley knows that
researchers won't have a cure for Alzheimer's today or even tomorrow. But
she hopes the genetic studies will uncover enough information about the
disease to help the next generation. "I know this can't help me," she says. "But maybe it can help my children or grandchildren." Copyright © 2002
Global Action on Aging |
