Alzheimer's, Dementia & Mental Health
Alzheimer’s Strikes First in Areas Where Cells
'Talk' Most; Boosts Plaque Accumulation
Sleep deprivation and increased stress, which may
affect Alzheimer’s risk, may also increase activity levels in these
Michael C. Purdy
Scientists have shown that brain
cells in the default mode network, highlighted in blue on the
left, communicate with each other more often than other brain
areas. This may help explain why these same areas are often hit
first by Alzheimer's plaques, which are highlighted in red in
the brain images on the right.
May 2, 2011 - Higher levels of cell chatter boost
amyloid beta in the brain regions that Alzheimer’s hits first,
researchers at Washington University School of Medicine in St. Louis
report. Amyloid beta is the main ingredient of the plaque lesions that
are a hallmark of Alzheimer’s, the disease most feared by senior
These brain regions belong to a network that is
more active when the brain is at rest. The discovery that cells in these
regions communicate with each other more often than cells in other parts
of the brain may help explain why these areas are frequently among the
first to develop plaques, according to the researchers.
Working with mice genetically engineered to develop
Alzheimer’s type-brain changes, scientists reduced the size and number
of plaques by decreasing brain cell activity in certain regions.
The results, appearing May 1 in Nature
Neuroscience, are the latest to hint at a resolution to lines of
evidence that have suggested busier brain cells can both contribute to
and prevent Alzheimer’s. According to a new theory, which brain cells
are kept busy may make all the difference.
Read the latest news on
Alzheimer's, Dementia & Mental Health
“Engaging the brain in tasks like reading,
socializing or studying may be helpful because they reduce activity in
susceptible regions and increase activity in regions that seem to be
less vulnerable to Alzheimer’s plaque deposition,” says David M.
Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of
the Department of Neurology.
“I suspect that sleep deprivation and increased
stress, which may affect Alzheimer’s risk, may also increase activity
levels in these vulnerable regions.”
The susceptible regions of the brain highlighted in
the new study belong to the default mode network, a group of brain
regions that become more active when the brain is not engaged in a
cognitively demanding task. Co-author Marcus Raichle, MD, professor of
neurology, of radiology and of neurobiology, was among the first to
describe the default mode network.
In a paper published in 2005, Washington University
researchers showed that regions in the default mode network are often
among the first to develop Alzheimer’s plaques. To understand why, Adam
Bero, a graduate student in Holtzman’s lab, analyzed the brain chemistry
of mice. He found that the mouse brain regions analogous to those in the
human default mode network had similarly high levels of early amyloid
plaque deposits when compared to other areas.
Next, Bero showed in younger mice that the
high-plaque regions had increased amyloid beta levels. In a third
experiment, he found that the greater amyloid beta levels were caused by
increased nerve cell communication in the affected regions.
To further prove the relationship between plaque
formation and cell communication, scientists trimmed the whiskers on one
side of a group of mice and kept them short for one month.
“Because mice are nocturnal and their eyesight is
poor, whiskers are an important way for them to sense where they are in
their environment,” Holtzman explains. “By cutting the whiskers back on
one side, we reduced neuronal activity in the region of the brain that
senses whisker movement.”
Loss of this input resulted in smaller and less
numerous plaques on the side of the brain connected to the pruned
whiskers. In a separate experiment, when researchers regularly
stimulated whiskers with a cotton swab, amyloid beta levels increased.
According to Holtzman, the results demonstrate the
direct connection between amyloid plaque formation and growth and
changes in brain cell activity levels in various parts of the brain. He
plans further investigations of the mechanisms that regulate default
brain activity, their connections to phenomena such as sleep, and their
potential effects on Alzheimer’s disease.
Funding for this study was from the National
Institutes of Health (NIH) and the Cure Alzheimer’s Fund supported this
Source: Bero AW, Yan P, Roh JH, Cirrito JR, Stewart
FR, Raichle ME, Lee J-M, Holtzman DM. Neuronal activity regulates the
regional vulnerability to amyloid-beta deposition. Nature Neuroscience,
May 1, 2011.
Washington University reports its School of
Medicine’s 2,100 employed and volunteer faculty physicians also are the
medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The
School of Medicine is one of the leading medical research, teaching and
patient care institutions in the nation, currently ranked fourth in the
nation by U.S. News & World Report. Through its affiliations with
Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine
is linked to BJC HealthCare.
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