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Progress Cited in
Alzheimer’s Diagnosis
By Andrew Pollack, The New York Times
October 15, 2007
Scientists reported progress yesterday toward one of medicine’s
long-sought goals: the development of a blood test that can accurately
diagnose Alzheimer’s disease, and even do so years before truly
debilitating memory loss.
A team of scientists, based mainly at Stanford University, developed a
test that was about 90 percent accurate in distinguishing the blood of
people with Alzheimer’s from the blood of those without the disease. The
test was about 80 percent accurate in predicting which patients with
mild memory loss would go on to develop Alzheimer’s disease two to six
years later.
Outside experts called the results, published online yesterday by Nature
Medicine, promising but preliminary. They cautioned that the work needed
to be validated by others and in much larger studies, because there have
been many disappointments in the past.
“Looking for biomarkers for Alzheimer’s disease is a very hot area,”
said Dr. William Jagust, professor of public health and neuroscience at
the University of California, Berkeley. “Things tend to get a lot of
attention, and they are not always borne out.”
Right now, Alzheimer’s disease is diagnosed by a battery of mental and
other tests, and even that diagnosis rests on the judgment of the
physician. Doctors say it would be useful to have something like a
pregnancy test for Alzheimer’s — one that is simple and definitive and
can pick up the disease early, maybe even before symptoms appear.
At present, treatments for Alzheimer’s disease are not very effective,
so some people might not want early notification that they have an
incurable ailment. But others might want it.
“There are people who want to know what their future holds, so they can
plan their estates and lives,” said Dr. Sam Gandy, a professor at Mount
Sinai School of Medicine in New York who is chairman of the medical and
scientific advisory council of the Alzheimer’s Association.
But the real usefulness of an early diagnostic test would come when
drugs are developed that slow or halt the progression of Alzheimer’s
disease. Several therapies that might be able to do that are now being
tested. The drugs would be most valuable if they could be used before
cognitive ability had declined too much.
Numerous efforts have been made to find an early marker in blood, urine,
spinal fluid and eye movements, as well as through brain imaging using
PET scans and M.R.I. A Norwegian company, DiaGenic, has presented some
early results of a blood test that analyzes gene activity. Researchers
at Cornell published early results last December using a pattern of 23
proteins in the spinal fluid. But no test has gained universal
acceptance. The closest is a test of two proteins in the spinal fluid
that is used in some European countries, said Dr. Dennis Selkoe, a
professor of neurology in Boston at Brigham and Women’s Hospital and
Harvard.
A blood test would be easier for patients than a spinal tap, Dr. Selkoe
said. But a blood test is possible only if Alzheimer’s disease leads to
changes outside the brain that can be detected in the blood.
Dr. Tony Wyss-Coray, an associate professor of neurology at Stanford and
the senior author of the new paper, said there was evidence from animal
studies that brains affected by Alzheimer’s sent out signals to the
body’s immune system. So his team decided that rather than looking at
all proteins in the blood, it would focus on those involved in
communication between cells, hoping to eavesdrop, as it were, on
dialogue related to Alzheimer’s.
The researchers gathered more than 200 blood samples from people with
Alzheimer’s and those without. Using 83 of the samples, they measured
the abundance of 120 proteins involved in cell signaling and found they
could distinguish the Alzheimer’s samples from the controls using 18 of
the proteins.
They then tested their 18-protein signature on an additional 92 samples.
The tests agreed with the clinical diagnosis about 90 percent of the
time.
Perhaps most intriguing were the results of the test on 47 blood samples
taken from people with mild cognitive impairment, a minor loss of memory
that can be a precursor of Alzheimer’s. The test was able to predict
with about 80 percent accuracy whether a patient went on to develop
Alzheimer’s two to six years after the blood sample had been collected.
Dr. Wyss-Coray, who is also at the Veterans Affairs Palo Alto Health
System, said that monitoring communications between cells might be a way
to develop diagnostic tests for other diseases. And understanding why
the levels of the 18 proteins are different in Alzheimer’s patients
might provide a better understanding of the disease.
The study was paid for by the National Institute on Aging, the John
Douglas French Alzheimer’s Foundation, the Alzheimer’s Association and
Satoris, a company co-founded by Dr. Wyss-Coray to commercialize the
test.
The company said in a news release that it hoped to have a test
available for research purposes next year. But even if the preliminary
results are validated, it is likely to be a few years before a test is
approved and ready for use by doctors.
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