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Study
suggests blood test for Alzheimer’s possible
Athens, Ga. – Researchers have revealed a
direct relationship between two specific
antibodies and the severity of Alzheimer’s
disease symptoms, raising hopes that a
diagnostic blood test for the devastating
disorder is within reach.
Researchers from the University of Georgia,
the Charlie Norwood VA Medical Center in
Augusta and the Medical College of Georgia
compared antibody levels in blood samples
from 118 older adults with the participant’s
level of dementia.
The team, whose results appear in the
current edition of Journal of Gerontology:
Medical Sciences, found that the
concentration of two specific proteins that
are involved in the immune response
increases as the severity of dementia
increases.
“We found a strong and consistent
relationship between two particular
antibodies and the level of impairment,”
said study co-author L. Stephen Miller,
professor and director of clinical
psychology training in the UGA Franklin
College of Arts and Sciences.
“The finding brings us closer to our
ultimate goal of developing a blood test
that can diagnose Alzheimer’s disease or
potentially identify if someone is at higher
risk for the disease.”
Miller’s co-authors include Jennifer S.
Wilson, a former undergraduate student in
the UGA Honors program who is now pursing
graduate studies at Emory University;
Shyamala Mruthinti, research pharmacologist
at the VA Medical Center and adjunct
professor at MCG; and Jerry Buccafusco,
director of the MCG Alzheimer’s Research
Center.
The team focused on antibodies that the body
creates in response to two proteins that are
associated with Alzheimer’s disease.
One protein, known as amyloid-beta, forms
the plaques that are evident in the brains
of people with Alzheimer’s upon autopsy.
The other protein, known as RAGE, is
involved in the normal aging process but is
expressed at higher levels in the brains of
people with Alzheimer’s.
In a previous study that compared a group of
people with Alzheimer’s disease to a healthy
control group, Mruthinti and her colleagues
found that anti-amyloid beta and anti-RAGE
antibodies are significantly higher in the
group with Alzheimer’s.
The team’s latest study expands on that
finding to reveal a direct relationship
between severity of Alzheimer’s disease and
levels of the two antibodies in the blood.
“Alzheimer’s is an inflammatory disease of
the brain, and these two antibodies give us
a way to measure that inflammation,”
Mruthinti said.
“Using them as an early diagnostic marker
may allow us to start drug treatment early,
when it’s most effective, to increase the
patient’s quality of life.”
While optimistic about their findings, the
researchers caution that it could still be
years before a diagnostic test based on
their work is clinically available.
The study found that the relationship
between the two antibodies and Alzheimer’s
severity persists even after controlling for
patient age and total antibody levels.
To further test the strength of the
relationship, the researchers are now
working with a sample that controls for
other factors that have the potential to
influence levels of the two antibodies, such
as diabetes and heart disease. Buccafusco
and his colleagues are also working to
decrease the cost and time involved in the
test.
“We’re in the process of trying to reduce
the test to a one-day procedure, whereas
right now it takes three to four days,”
Buccafusco said.
“But even now, our test is orders of
magnitude cheaper than having people come in
every few months to get a functional MRI or
PET scan to try to discern brain plaques.”
The team is targeting the two proteins
themselves as a possible treatment for
Alzheimer’s disease. Mruthinti explains
that, individually, amyloid-beta and RAGE
proteins don’t provoke an immune response.
The trouble begins when the two bind and the
immune system attacks, resulting in constant
state of inflammation that damages the
brain.
The researchers recently developed a way to
measure levels of amyloid beta-RAGE complex,
and preliminary data using transgenic mice
that express Alzheimer’s symptoms suggest
that an antigen they created to boost the
body’s natural immune response to the
complex can reduce the formation of the
brain plaques.
“The amyloid beta-RAGE complex cuts off the
connections between neurons,” Mruthinti
explained, “but our hope is that we can
protect those connections by preventing
those plaques from forming.”
The research was funded by a Merit Review
Award from the Veterans Administration to
principal investigator Mruthinti and by the
Medical College of Georgia Alzheimer’s
Research Center
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