Research Suggests Stress Hormones Play A Central Role In The Development And
Progression Of Alzheimer's
http://www.medicalnewstoday.com/medicalnews.php?newsid=50787&nfid=crss
Main Category: Anxiety News
Article Date: 31 Aug 2006 - 21:00pm
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Stress hormones appear
to rapidly exacerbate the formation of brain lesions that are the hallmarks of
Alzheimer's disease, according to researchers at UC Irvine. The findings suggest
that managing stress and reducing certain medications prescribed for the elderly
could slow down the progression of this devastating disease.
In a study
with genetically modified mice, Frank LaFerla, professor of neurobiology and
behavior, and a team of UCI researchers found that when young animals were
injected for just seven days with dexamethasone, a glucocorticoid similar to the
body's stress hormones, the levels of the protein beta-amyloid in the brain
increased by 60 percent. When beta-amyloid production increases and these
protein fragments aggregate, they form plaques, one of the two hallmark brain
lesions of Alzheimer's disease. The scientists also found that the levels of
another protein, tau, also increased. Tau accumulation eventually leads to the
formation of tangles, the other signature lesion of Alzheimer's. The findings
appear in this week's issue of the Journal of Neuroscience.
"It is
remarkable that these stress hormones can have such a significant effect in such
a short period of time," LaFerla said. "Although we have known for some time
that higher levels of stress hormones are seen in individuals in the early
stages of Alzheimer's, this is the first time we have seen how these hormones
play such a direct role in exacerbating the underlying pathology of the
disease."
The researchers injected four-month-old transgenic mice with
levels of dexamethasone similar to the level of hormones that would be seen in
humans under stress. At this young age, there would be little formation of
plaques and tangles in the brains of the mice. After one week, the scientists
found that the level of beta-amyloid in the brains of the animals compared to
what is seen in the brains of untreated eight- to nine-month-old mice,
demonstrating the profound consequence of glucocorticoid exposure. When
dexamethasone was given to 13-month-old mice that already had some plaque and
tangle pathology, the hormone again significantly worsened the plaque lesions in
the brain and led to increased accumulation of the tau protein.
"Although we expected that this drug, which, like the stress hormone
cortisol, activates glucocorticoid receptors, might have some effect on plaques
and tangles, it was surprising to find that such large increases were induced in
relatively young mice," said James L. McGaugh, research professor of
neurobiology and behavior and co-author of the paper.
The increased
accumulation of beta-amyloid and tau appears to work in a "feedback loop" to
hasten the progression of Alzheimer's. The researchers found that the higher
levels of beta-amyloid and tau led to an increase in the levels of the stress
hormones, which would come back to the brain and speed up the formation of more
plaques and tangles.
According to the researchers, these findings have
profound implications for how to treat the elderly who suffer from Alzheimer's
disease.
"This study suggests that not only is stress management an
important factor in treating Alzheimer's disease, but that physicians should pay
close attention to the pharmaceutical products they prescribe for their elderly
patients," said Kim Green, a postdoctoral researcher in neurobiology and
behavior and first author of the paper. "Some medications prescribed for the
elderly for various conditions contain glucocorticoids. These drugs may be
leading to accelerated cognitive decline in patients in the early stages of
Alzheimer's."
Alzheimer's disease is a progressive neurodegenerative
disorder that affects 4.5 million to 5 million adults in the United States. If
no effective therapies are developed, it is estimated that 13 million Americans
will be afflicted with the disease by 2050.
In recent years, LaFerla has
been at the forefront of Alzheimer's research. He and other members of his
research team developed the transgenic mice used in this study, which are now a
model for studying Alzheimer's around the world. Earlier this year, he announced
work on a new compound that not only relieves the cognitive symptoms of
Alzheimer's disease, but also reduces the plaques and tangles in the brain.
###
Lauren Billings, postdoctoral researcher, and Benno
Roozendaal, assistant researcher in neurobiology and behavior, collaborated on
the study. The work was funded by grants from the Alzheimer's Association, the
National Institutes of Health and the National Institute of Mental Health.
About the University of California, Irvine: The University of
California, Irvine is a top-ranked university dedicated to research, scholarship
and community service. Founded in 1965, UCI is among the fastest-growing
University of California campuses, with more than 24,000 undergraduate and
graduate students and about 1,400 faculty members. The second-largest employer
in dynamic Orange County, UCI contributes an annual economic impact of $3.3
billion. For more UCI news, visit http://www.today.uci.edu/
UCI maintains an online
directory of faculty available as experts to the media. To access, visit
www.today.uci.edu/experts.
Video news release available Quicktime: http://www.uci.edu/experts/video_news.php?src=laferla
Sound bites and b-roll available upon request. Photos available at http://today.uci.edu/news/release_detail.asp?key=1514
Contact: Farnaz Khadem
University of California - Irvine