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Preliminary New Blood Test to detect
Alzheimer’s Disease uncovered
Newswise — DALLAS – Feb. 14, 2011 – UT
Southwestern Medical Center scientists have
helped develop a novel technology to
diagnose Alzheimer’s disease from blood
samples long before symptoms appear.
This
preliminary technology, which uses synthetic
molecules to seek out and identify
disease-specific antibodies, also could be
used eventually in the development of
specific biomarkers for a range of other
hard-to-diagnose diseases and conditions,
including Parkinson’s disease and immune
system-related diseases like multiple
sclerosis and lupus, the researchers
predict.
“One of the
great challenges in treating patients with
Alzheimer’s disease is that once symptoms
appear, it’s too late. You can’t un-ring the
bell,” said Dr. Dwight German, professor of
psychiatry and an author of the paper
published in the Jan. 7 edition of Cell.
“If we can find a way to detect the disease
in its earliest stages – before cognitive
impairment begins – we might be able to stop
it in its tracks by developing new treatment
strategies.”
Because
patients with Alzheimer’s disease (AD)
exhibit immune system activation and
neurodegeneration in several brain regions,
researchers in the study hypothesized that
there may be numerous antibodies in the
serum of affected patients that are specific
to the disease and can serve as a biomarker.
Antigens –
substances such as protein from a virus or
bacteria that triggers an immune response –
traditionally have been necessary for the
discovery of antibody biomarkers. It has
been impossible previously to identify an
antibody (a type of targeted immune
molecule) without first knowing the antigen
that triggers its production.
The new study,
however, challenges conventional wisdom and
uses synthetic molecules (peptoids) rather
than antigens to successfully detect signs
of disease in patients’ blood samples. These
peptoids have many advantages; they can be
modified easily and can be produced quickly
in relatively large amounts at lower cost.
The adaptive
immune system is thought to be a rich source
of protein biomarkers, but diagnostically
useful antibodies remain undiscovered for a
large number of diseases, Dr. German said.
This is, in part, because the antigens that
trigger an immune response in many diseases
are unknown. The technology behind this
discovery is essentially an immune-system
reader, which is designed to pick out
antibodies without knowing in advance which
ones to look for.
The
researchers used a combination library of
several thousand peptoids to screen serum
samples from mice with multiple
sclerosis-like symptoms as well as from
healthy control mice.
The particular peptoids that retained more
antibodies from the blood samples of the
diseased animals were identified as
potential agents for capturing
diagnostically useful molecules.
The
investigators then examined serum samples
from six AD patients, six healthy patients
and six patients with Parkinson’s. Three
peptoids were identified that captured six
times the IgG antibody levels in all of the
Alzheimer’s patients when compared to the
control group or to the Parkinson’s
patients.
Two of the peptoids were found to bind the
same IgG antibody, while the third was shown
to bind to different antibodies – meaning
there are at least two candidate biomarkers
for AD.
Using an additional set of 16 normal control
subjects and 10 subjects at the very early
state of AD, the three candidate biomarkers
identified AD with 90 percent accuracy.
“The results
of this study, though preliminary, show
great potential for becoming a landmark,”
said Dr. German.
Other UT
Southwestern researchers involved in the
study were Dr. Ramon Diaz-Arrastia,
professor of neurology and neurotherapeutics;
Steven Connell, research technician; and Dr.
Linda Hynan, professor of clinical sciences.
Others include
senior author and former UT Southwestern
faculty member Dr. Thomas Kodadek, now at
Scripps Florida Research Institute; Dr. Anne
Gocke, former postdoctoral fellow in
translational medicine; and researchers with
Opko Health Laboratories.
Funding was
provided by the National Institutes of
Health.
Visit http://www.utsouthwestern.org/neurosciences to
learn more about UT Southwestern’s clinical
services in neurosciences, including
psychiatry.
