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Brain Plaques linked to increased
Newswise — Scientists have long assumed that
amyloid brain plaques found in autopsies of
Alzheimer's patients are harmful and cause
Alzheimer's disease. But autopsies of people
with no signs of mental impairment have also
revealed brain plaques, challenging this
Now, for the first time, researchers at
Washington University in St. Louis have
shown that brain plaques in apparently
healthy individuals are associated with
increased risk of diagnosis with Alzheimer's
disease years later.
In two studies published this month in
Archives of Neurology, scientists report
that volunteers with brain plaques were more
likely to have declining scores on annual
cognitive tests, to show signs of shrinkage
in a key brain area affected by Alzheimer's
and to eventually be diagnosed with the
"We don't have enough data yet to
definitively say that people who scan
positive for these brain plaques have
presymptomatic Alzheimer's disease, but
something is clearly going on that does not
bode well for the health of their aging
brains," says John C. Morris, the Harvey A.
and Dorismae Hacker Friedman Distinguished
Professor of Neurology and director of
Washington University's Alzheimer's Disease
Research Center (ADRC) and the Friedman
Center for Aging.
Morris and others at the ADRC have
previously found evidence that Alzheimer's
disease harms the brain for years prior to
They are pushing for earlier diagnosis as an
essential step to successful treatment of
Alzheimer's disease, but to do that they
first have to seek earlier indicators of
disease and then wait years to see if people
with the indicators later develop
According to Morris, the new papers are
early and encouraging indicators that
scientists are on track to pushing back the
time at which diagnosis can be made.
"We only have a very small number of
subjects to date, but what we're learning so
far has been consistent with our
predictions," he says.
The new studies were made possible by the
development of an imaging agent, Pittsburgh
Compound B (PiB), that lets scientists use
positron emission tomography scans to detect
amyloid plaques in living brains for the
Prior to PiB, clinicians could only verify
the presence of brain plaques during
autopsies. PiB scanning of ADRC research
participants is directed by Mark Mintun,
M.D., vice chair for research in radiology
and professor of radiology at the
University's Mallinckrodt Institute of
Martha Storandt, Ph.D., professor of
psychology and of neurology, led one of the
studies, which compared a variety of factors
in plaque-positive and plaque-negative
"One of the main things we wanted to know
was whether people who scanned positive for
brain plaques scored abnormally low on
cognitive tests," she says.
didn't, but when we looked at their annual
testing records over a period of years, we
saw that the scores of the plaque-positive
group were declining, while those of the
plaque-negative group were not."
Magnetic resonance imaging scans analyzed by
Denise Head, Ph.D., assistant professor of
psychology, revealed that brain areas hit
hard by Alzheimer's disease, such as the
parahippocampal gyrus, were smaller in
subjects with plaques.
In a second study, led by Morris,
researchers tracked a group of 159
volunteers, ages 51 to 88, who were scanned
using PiB between 2004 and 2008. At the time
of the scans, none of the participants
showed signs of mental impairment.
Twenty-three of the volunteers later
developed mild impairment, and nine members
of that group were diagnosed with
Those who stayed mentally healthy did not
scan positive for plaques, but volunteers
later diagnosed with problems did.
Comparisons of the volumes of key brain
structures revealed the same disparities
seen in the other study: subjects who
developed mental impairment had significant
reductions in their parahippocampal gyrus
and other structures affected by
According to Morris, a parallel effort at
Washington University that analyzes
cerebrospinal fluid to diagnose Alzheimer's
earlier is also meeting with early success.
That program is led by David Holtzman, M.D.,
the Andrew and Gretchen Jones Professor and
chair of the Department of Neurology and
Anne Fagan, Ph.D., research associate
professor of neurology.
Morris speculates that earlier diagnosis and
testing of new treatments may be possible
within the next 10 years.
"There are risks inherent in Alzheimer's
treatments, so we have to be careful that
healthy people who are selected to receive
these treatments to prevent dementia caused
by Alzheimer’s disease really do have
presymptomatic disease," he says.
Funding from the National Institute on Aging
and the Charles and Joanne Knight
Alzheimer's Research Initiative supported
Washington University 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 third 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.