18 proteins ID at-risk patients years before clinical diagnosis, scientists say
MONDAY, Oct. 15 (HealthDay News) -- An international team of scientists has developed a blood test that could reveal which patients with mild cognitive impairment will go on to develop Alzheimer's disease.
If replicated and validated -- and assuming the development of effective treatments against Alzheimer's in the future -- such a test could open the door to medicating at-risk patients earlier and slowing or limiting neurological damage, explained Dr. Allan Levey, chair of neurology at Emory University, Atlanta.
"If it can be replicated, then we will find out how important [the study] really is," said Levey, who was not involved in the research.
The findings were published in the Oct. 14 online issue of Nature Medicine.
According to the Alzheimer's Association, Alzheimer's is a progressive, fatal brain disease that affects almost one in eight individuals over the age of 65.
Yet there currently exists no early diagnostic screen for Alzheimer's disease. Diagnosis today is based not on blood chemistry, but on a combination of psychological and imaging tests. Many of those who present with mild cognitive impairment (MCI), will ultimately develop Alzheimer's disease, but others never do.
"Currently, it's very difficult to know who will progress to Alzheimer's and who will progress to other diseases, or which won't progress at all," said Levey. "Ideally, one wants to be able to know at the stage of mild cognitive impairment, or even earlier, if someone is destined to get Alzheimer's disease."
In the new study, a group led by Tony Wyss-Coray, an associate professor of neurology at the Stanford University School of Medicine, analyzed 259 blood samples obtained from individuals with and without Alzheimer's disease. They focused on 120 proteins involved in cellular signaling and communication.
The team identified 18 proteins in particular whose abundance could distinguish those with Alzheimer's disease from those without it, for an overall accuracy of about 90 percent -- that is, it correctly classified individuals who had been clinically diagnosed with Alzheimer's disease 95 percent of the time and classified as negative those without the disease 83 percent of the time.
This panel of proteins was equally effective when applied to another, completely separate set of patient samples, the researchers noted.
But "the home run of the paper," said Levey, was the finding that, when applied to blood samples collected from patients who were diagnosed with mild cognitive impairment -- a condition that often, but not always, precedes Alzheimer's -- the panel could predict who would ultimately develop Alzheimer's with 81 percent accuracy, 30 months before clinical diagnosis, on average.
Calling the study "very interesting," Levey nevertheless noted two caveats. The first was its relatively small sample size. The other was its use of proteins that have no obvious relationship to Alzheimer's.
"The blood has thousands of proteins, and they started with 120 proteins that they could measure," he said. "I don't think if one were to try to make a biomarker for Alzheimer's that you would necessarily choose these 120 proteins."
Wyss-Coray agreed that the team's decision to focus specifically on signaling proteins might seem like "a bit of a crazy idea." But given the disease's target organ, it makes sense, he said.
"Cells receive input through hundreds of different receptors, and it responds with some output, usually a signaling protein," Wyss-Coray explained. "So, by thinking in terms of this output, we decided to look specifically at signaling proteins and see if there are changes between patients who are healthy versus those with Alzheimer's disease or other dementias."
Others have also made progress in the development of early diagnostic tests for Alzheimer's. At the Alzheimer's Association's International Conference on Prevention of Dementia, in June, for instance, one group described a candidate test based on gene expression levels in blood.
"It's exciting to see this sort of work progress," said Dr. Sam Gandy, chair of the Alzheimer's Association's Medical and Scientific Advisory Council. "The important next step is to be sure that the report can be independently replicated."
Should that happen, Gandy said, patients would not be the only beneficiaries; the drug-development industry could use this assay to help select patient populations for trials of drugs to prevent -- as opposed to treat -- Alzheimer's disease.
"Because we don't have a marker that predicts [Alzheimer's] right now, such a trial is almost prohibitively expensive," he said -- "easily 10 times" the estimated $50 million required for standard clinical trials.
For more on Alzheimer's Disease, visit the Alzheimer's Association.
SOURCES: Tony Wyss-Coray, Ph.D., associate professor, neurology, Stanford University School of Medicine, Stanford, Calif.; Allan Levey, M.D., Ph.D., chairman, department of neurology, Emory University, Atlanta; Sam Gandy, M.D., Ph.D., chairman, Alzheimers Association Medical & Scientific Advisory Council; Oct. 14, 2007, Nature Medicine online
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