Eduardo Jose Bernardino

One of the most distressing aspects of memory loss for older adults is how hard it is to determine the cause. The question looms: Is it Alzheimer’s? But now Stanford researchers have developed a blood test that is a step toward answering that question two to six years before the onset of the disease.

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’ conversations and the changes in the brain accompanying Alzheimer’s. They found that 90 percent of the time the blood test could indicate who had been diagnosed with Alzheimer’s and could predict 91 percent of the time 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,” says Tony Wyss-Coray, PhD, associate professor of neurology and neurological sciences and senior author of the study, which appeared in the Oct. 14, 2007, advance online edition of Nature Medicine. “It’s not that the cells are using new words when something goes wrong. It’s just that some words are much stronger and some are much weaker; the chatter has a different tone.”
No test yet

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, 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.

The blood-test concept began when Wyss-Coray and his collaborators measured levels of 120 different proteins used by cells to communicate to see if any of them could be indicators for Alzheimer’s. After developing an analysis procedure to recognize any patterns, the researchers discovered that as few as 18 proteins were sufficient to identify an Alzheimer’s-specific pattern.

Among blood samples from 92 individuals whose symptoms ranged from none to full dementia, the protein analysis matched the clinical diagnosis 90 percent of the time. The researchers 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.

Satoris Inc., a company that Wyss-Coray co-founded, plans to develop a commercial Alzheimer’s blood test, initially for use in research labs.

This study was funded by the John Douglas French Alzheimer’s Foundation, the Alzheimer’s Association, the U.S. National Institute of Aging and Satoris Inc.