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Detecting Alzheimer's Early
Scientists Make Progress
Toward Test for the Disease:
Clues in Blood and Spinal Fluid
By Gautam Naik, New York Times
December 12, 2006
The amount of cholesterol in the blood is usually a good indicator of a person's risk of suffering heart disease. Now scientists are making headway in developing a similar test to detect the earliest stages of Alzheimer's disease.
Over the past two years, rival scientists in the U.S. and Europe have identified a series of proteins, known as biomarkers, whose presence in blood or spinal fluid may indicate whether a patient has Alzheimer's, the most common form of dementia. In the short term, that could lead to better and earlier diagnosis of Alzheimer's patients. In the longer term, it could yield more-effective drugs and even reduce the cost of developing them.
The search for Alzheimer's biomarkers "is a hot field, and the goal is a very big one," says Simon Lovestone, a professor of geriatric psychiatry at King's College London, who led a team that recently found two such biomarkers in blood. "It's a step along the way to better treatment."
Both the European Commission and the U.S. National Institutes of Health are funding large-scale projects on Alzheimer biomarkers. In a new paper appearing today in the Annals of Neurology, researchers from Cornell University in Ithaca, N.Y., and Weill Cornell Medical College in New York describe how they have identified 23 biomarker proteins for Alzheimer's in a trial of nearly 100 patients. The results need to be replicated in a larger clinical trial -- and plenty of challenges remain before the findings can become the basis for a reliable clinical test.
Still, the study is a "good start," says Susan Molchan, who leads a new $60 million project at the NIH's National Institute on Aging, which is also seeking to identify Alzheimer's biomarkers. "We want to identify patients earlier and treat them earlier," she adds. Dr. Molchan has read the Annals of Neurology paper but wasn't involved in the research.
Alzheimer's is a progressive brain disorder that can cause memory lapses, fuzzy thinking and difficulty in performing simple activities, such as dialing a phone number. Existing drugs only treat symptoms; there is no cure. About four million mostly elderly Americans have the disease. As the population ages, the figure is expected to soar to about 14 million by 2050, unless new ways are found to prevent or treat the illness, according to the NIH.
Diagnosing Alzheimer's can be tricky, especially in the early course of the illness when many of its symptoms -- such as mild forgetfulness -- resemble those of other maladies, such as depression or stress, or the natural aging process. That's why most neurologists can only diagnose "possible" or "probable" Alzheimer's. The only foolproof way to verify the existence of the disease is to study the brain after death.
A biomarker-based test holds the promise of an early diagnosis for Alzheimer's. It would enable patients to be treated at the initial stages of their illness, when they are most likely to respond. Families would also have the chance to discuss care options with patients while they are still able to participate in the decisions.
A biomarker protein is a telltale chemical fingerprint that can be detected in parts of the body, such as blood or spinal fluid. If biomarkers for Alzheimer's are found in a person's spinal fluid, for example, they can confirm a diagnosis of the disease. Better yet, "if you know how these markers change as the disease progresses, you might be able to alter them" with a drug, thus stalling or reversing the course of the illness, says Norman Relkin, a professor at Weill Cornell Medical College and a co-author of the latest study.
For several years, doctors in European countries -- especially Sweden -- have extracted spinal fluid from symptomatic patients and tested it for three biomarker proteins that appear to indicate the existence of Alzheimer's. At the same time, they use brain scans and other tests to exclude other cognitive disorders.
In February, Swedish scientists published a five-year study in the journal Lancet Neurology, describing how the relative progression to Alzheimer's disease in patients with mild cognitive impairment was significantly increased if their spinal fluid contained abnormal amounts of the same three biomarker proteins, known as b-amyloid, total tau and
phosphorylated-tau.
In October, researchers from King's College London and their collaborators, Proteome Sciences PLC, said they had discovered 15 protein biomarkers associated with Alzheimer's in patients' blood.
Two of these proteins, involved in an inflammation response, may play an especially significant role in the disease, the researchers say. Their findings, based on blood tests from 500 U.K. patients, appeared in the journal Brain. The next step: The scientists hope to verify the data in a larger trial and see whether the two proteins can be used to predict how Alzheimer's disease progresses.
Researchers in the U.S. are also involved in the quest for Alzheimer biomarkers. In February 2005, scientists at Northwestern University claimed that they had become one of the first to detect a significant biomarker for the disease in living patients. They found tiny amounts of a toxic protein, ADDL, in the spinal fluid of living Alzheimer's patients. Previous research had suggested that ADDL may accumulate at the beginning of the illness and block memory function. The findings appeared in the Proceedings of the National Academy of Sciences. Nanosphere Inc., a biotechnology firm in Northbrook, Ill., that was spun off from Northwestern, hopes to use the results to develop a diagnostic test.
The new paper appearing in the Annals of Neurology may be the farthest-reaching one so far. Researchers compared 2,000 proteins in patients with Alzheimer's and in those without. As a result, they homed in on 23 proteins that seemed strongly associated with the disease.
"My most-conservative estimate is that it will take three to five years before a test like this can be translated into clinical practice," says Dr. Relkin.
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