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Alzheimer's, Dementia & Mental Health
Blood Test Coming Very Close to Predicting
Alzheimer’s Risk
Tests reaching above 90 percent in accuracy
Oct. 15, 2007 - One of the most distressing aspects
of Alzheimer's disease is the difficulty in determining whether mild
memory problems, which seem to plague most senior citizens, are the
beginning of an inevitable mental decline. Researchers at the Stanford
University School of Medicine have developed a blood test that is a step
toward giving people an answer two to six years in advance of the onset
of the disease.
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Alzheimer's, Dementia & Mental Health |
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The test identifies changes in a handful of
proteins in blood plasma that cells use to convey messages to one
another. The research team discovered a connection between shifts in the
cells' dialog and the changes in the brain accompanying Alzheimer's.
They found that the blood test could indicate who had Alzheimer's with
90 percent agreement with clinical diagnoses, and could predict the
onset of Alzheimer's two to six years before symptoms appeared.
"Just as a psychiatrist can conclude a lot of
things by listening to the words of a patient, so by 'listening' to
different proteins we are measuring whether something is going wrong in
the cells," said Tony Wyss-Coray, PhD, associate professor of neurology
and neurological sciences and senior author of the study.
"It's not that the cells are using new words when
something goes wrong," said Wyss-Coray. "It's just that some words are
much stronger and some are much weaker; the chatter has a different
tone."
The study will appear in the Oct. 15 advance online
edition of Nature Medicine.
"I really think it has enormous potential," said
Lennart Mucke, MD, director and senior investigator of the Gladstone
Institute of Neurological Disease at the University of California-San
Francisco, who did not participate in the study. "Most researchers in
this field agree that there is an urgent need for better lab tests for
Alzheimer's disease, and this study has addressed this need admirably."
Listening to cells' messages may not only lead to
the first noninvasive diagnostic test for Alzheimer's; it could also
lead to similar discoveries about other disorders by focusing on what
cells use to talk to each other, said Wyss-Coray, who is part of the
Geriatric Research, Education and Clinical Center at the Veterans
Affairs Palo Alto Health Care System.
Currently, the clinical diagnosis for Alzheimer's
is one of exclusion - by testing for other causes of memory loss and
cognitive declines, such as stroke, tumors and alcoholism. If those
conditions are eliminated as causes of memory loss, what remains is
Alzheimer's, which is the most common cause of dementia. Even the
clinical diagnosis is imperfect, and the only definitive diagnosis is by
brain autopsy after a person has died.
According to the Alzheimer's Association, more than
5 million Americans are afflicted with the disease, which robs patients
of memory, thinking and the ability to communicate.
The blood-test concept began when Wyss-Coray and
Sandip Ray, one of the two first authors of the paper, collaborated to
measure levels of 120 different proteins used by cells to communicate to
see if any of them could be indicators for Alzheimer's.
At the time the work was done, Ray was an employee
of Satoris Inc., a company co-founded by Ray, Wyss-Coray and Yuen So,
MD, PhD, professor of neurology and neurological sciences. Wyss-Coray is
a consultant for Satoris Inc.
Ray used blood samples from five people diagnosed
with Alzheimer's, and compared those to samples from five people who
didn't have the disease. He found a number of proteins used for
communication that demonstrated striking differences between the two
groups.
Markus Britschgi, PhD, a postdoctoral scholar in
Wyss-Coray's lab, became intrigued with the idea that proteins used by
cells to communicate could be measured in the blood to indicate what is
going on in the body - including the brain.
"This study made me realize that we should get away
from this image of a brain isolated from the body," said Britschgi, who
is also a first author of the paper. "The brain is part of the body and
so it's connected in one huge network."
Reaching out to clinics in the United States, as
well as Sweden, Poland and Italy, Britschgi obtained a total of 259
archived blood samples from individuals who had symptoms ranging from
nothing abnormal to mild cognitive impairment to advanced Alzheimer's.
Starting with 120 communication proteins, the team developed an analysis
procedure to recognize if there was a pattern seen in Alzheimer's that
could be compared with that of people without the condition. They
discovered that as few as 18 proteins were sufficient to identify an
Alzheimer's-specific pattern.
Among blood samples from 92 individuals who ranged
from no symptoms to full dementia, the protein analysis matched the
clinical diagnosis 90 percent of the time.
They then asked if they could predict the
development of Alzheimer's among 47 people with mild cognitive
impairment who had been followed from two to six years. The test - done
on blood samples taken several years earlier - flagged 91 percent of the
patients who developed Alzheimer's by the end of the follow-up time, as
diagnosed by conventional methods.
"Already we have people approaching us at meetings
asking if they can give us a vial of their grandfather's blood for
testing," said Britschgi. Their findings show that it is possible to use
factors in the blood to diagnose and even predict the disease, but, the
authors emphasized, it must now be confirmed in other labs.
According to Satoris Inc, the company will develop
a commercial Alzheimer's blood test, initially for use in research labs
and, if confirmed as reliable, eventually as a clinical diagnostic test
upon regulatory approval.
Britschgi and Wyss-Coray are interested in finding
out why the cell communication pathways are altered in Alzheimer's. In
their study, they determined that the 18 proteins that indicate
Alzheimer's are also involved in the production of new blood cells,
immune processes and apoptosis, the process of programmed cell death
when a cell is no longer needed.
"Our hypothesis is that there is something wrong
with the production of certain blood cells, which may be needed to clear
that stuff that accumulates in the brain in Alzheimer's disease," said
Wyss-Coray. "That makes a lot of sense, and it is very exciting to think
of immune cells and molecules interacting with the brain."
Mucke, the director of Gladstone, added, "It will
be interesting to find out in clinical trials if the identified disease
markers are also useful for monitoring the response of individual
patients to therapeutic interventions. That would be tremendous."
Of the 25 authors included on this paper, six other
contributors from Stanford are included. They are: Yoshiko Takeda-Uchimura,
a research associate in Wyss-Coray's laboratory; Leah Friedman, PhD,
senior research scholar in psychiatry and behavioral sciences; William
Robinson, MD, PhD, assistant professor of medicine; Jared Tinklenberg,
MD, professor of psychiatry and behavioral sciences; Jerome Yesavage,
MD, professor of psychiatry and behavioral sciences; and Robert
Tibshirani, PhD, professor of health research and policy and of
statistics. Tibshirani is also a consultant for Satoris Inc.
Editor’s Notes:
This study was supported by the John Douglas French
Alzheimer's Foundation, the Alzheimer's Association, the U.S. National
Institute of Aging and Satoris Inc.
Stanford University Medical Center integrates
research, medical education and patient care at its three institutions -
Stanford University School of Medicine, Stanford Hospital & Clinics and
Lucile Packard Children's Hospital at Stanford. For more information,
please visit the Web site of the medical center's Office of
Communication & Public Affairs at
http://mednews.stanford.edu.
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