The work provides yet another motivation for combating obesity
and the growing diabetes epidemic it is fueling in the United
States. It also suggests that onset of Alzheimer's could be
delayed or even prevented in some people if they don't become
diabetic earlier in life, said David Schubert, the lead
investigator and professor at the institute's Cellular
Neurobiology Laboratory.At least 21 million people in the United States have diabetes
and about 54 million have prediabetes. Nearly 5 million Americans
suffer from Alzheimer's, and virtually all of them are 65 or
older. "The important point to make is not to get obese and
develop diabetes," Schubert said. "It's a warning signal. It
emphasizes that you don't want to get diabetes when you're young."
The analysis led by Schubert is published in the online edition
of the medical journal Neurobiology of Aging. The study was
co-authored by fellow Salk researchers Joseph Burdo and Qi Chen
and diabetes expert Nigel Calcutt, who teaches in the pathology
department at the University of California San Diego. The
researchers are based in San Diego.
Besides offering an explanation for the combination of diabetes
and Alzheimer's in some individuals, the report suggests that
people at risk of developing Alzheimer's could benefit from
consuming foods and supplements rich in antioxidants, including
fish, beans, berries, vegetables, fish oil and vitamin E, said
researchers such as Greg Cole, associate director of the
University of California Los Angeles Alzheimer's Center.
Antioxidants can help fight advanced glycation, the buildup of
certain toxic protein molecules that can harm some blood vessels
and lead to destructive inflammation of the brain. Developing
drugs to treat and cure Alzheimer's requires huge investments of
time and money, Cole said, so studies that rely on animal subjects
- like the one by the Salk and UCSD researchers - fill an
important gap.
"There's sort of an urgent need to move ahead with prevention,"
he said. "Since we have an obesity epidemic driving diabetes rates
up and intersecting with an aging population, we're looking at
having even more cases (of Alzheimer's) than we might have
expected. "For more than a decade, scientists have been building
an increasingly convincing case for a relationship between
diabetes and Alzheimer's in some patients.
Several recent studies have shown that people with Type 2
diabetes, the version most associated with obesity, have a 30
percent to 65 percent higher chance of developing Alzheimer's than
non-diabetics. Diabetes centers on insulin, a hormone produced by
the pancreas that helps to move glucose - a simple sugar - to
cells throughout the body. Glucose is the body's main fuel, and
cells die when they can't get enough of it.
In diabetics, the insulin process breaks down and sugar levels
build up in the bloodstream. Type 1 diabetics can't produce
insulin, while Type 2 diabetics often don't make enough of the
hormone and can't process it properly.
Some researchers have suggested that in a way, Alzheimer's
might be another type of diabetes.
In October, for example, researchers at Northwestern University
said they had found cells in the brains of Alzheimer's patients
that were resistant to insulin.
While most previous studies focused on people already suffering
from Alzheimer's, the Salk researchers sought to investigate the
effects of diabetes before symptoms of the brain disease appear.
Schubert and his colleagues triggered diabetes in young mice that
were genetically predisposed to develop Alzheimer's later in life.
Seven weeks later, the mice were placed in a shallow pool of water
with an escape platform hidden 1 centimeter below the surface.
Researchers measured the time it took the mice to find the
platform. The test was repeated twice a day for eight days to
measure the rodents' memory and learning ability.
Over the course of the study, the mice that were both diabetic
and prone to developing Alzheimer's had a more difficult time
finding the platform than those with one disease or the other.
When the researchers examined the brains of all the rodents, they
found significantly greater amounts of the toxins linked to
advanced glycation in the mice with diabetes and the
predisposition for Alzheimer's. These toxins are typically found
in large quantities in the brains of mice with fully developed
Alzheimer's.
Now that the Salk and UCSD researchers have identified the
mechanics of how diabetes triggers the onset of Alzheimer's
symptoms in young mice, they hope to use the rodents to test a
pair of drugs being developed to treat Alzheimer's in people,
Schubert said. "If a drug worked in a (research) model that we
have," he said, "then I think it would be very useful for adult
onset Alzheimer's."
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