Alzheimer's, Dementia & Mental Health
Protein Discovery May Lead to Blood Test to Detect
Alzheimer’s Disease
Two specific proteins appears to determine the
severity of Alzheimer’s disease
March
11, 2009 - The concentration of two specific proteins appears
to determine the severity of Alzheimer’s disease symptoms, research say.
This discovery raises hopes, they say, that a diagnostic blood test for
the devastating mental 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.
Antibodies - a protein produced by B cells in the
body in response to the presence of a bacterium or virus - are a primary
form of immune response in resistance to disease and act by attaching
themselves to a foreign antigen and weakening or destroying it.
“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.”
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.
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.
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.
Original report by Sam Fahmy, University of
Georgia
