Alzheimer’s disease begins to damage the brain years before the first symptoms appear. Scientists are furiously searching for a way of picking up the devastating disorder in those first stages, in the hope that prompt treatment might slow its progression and perhaps someday, with new treatments, stop it altogether.
Now a California company says that it will soon be able to offer a simple blood test that can detect Alzheimer’s disease in its early stages, or perhaps even predict its onset. The test picks up a protein signature in the blood that researchers say is specific to Alzheimer’s.
“We appear to be able to detect it about two years earlier than clinicians,” says Cris McReynolds, president and CEO of Satoris, based in Redwood City, CA. The company was founded in 2003 to develop and commercialize blood-based tests for Alzheimer’s disease.
The Satoris test is nearly 90 percent accurate in identifying people with mild cognitive impairment that progressed to Alzheimer’s disease several years later, according to a study published last year in Nature Medicine by Satoris researchers and others in the United States and Europe. The study “made a splash,” according to Maria Carrillo, director of medical and scientific relations for the Alzheimer’s Association. Satoris is now working with collaborators including the Mayo Clinic to validate that data, and the company expects to make the test available to researchers by the end of the year. After that, the company plans to conduct clinical trials and seek FDA approval for a test kit that could be used in clinical settings.
If the test makes it to the market, “that could be a major advance,” says Neil Buckholtz, chief of the National Institute on Aging’s Dementias of Aging branch. (Buckholtz was not involved in the work.) “If we can pick up those changes in the brain at the beginning of the disease process, and we could have drugs that could slow or stop that process, that’s really what we’re trying for,” he says.
At the moment, Alzheimer’s can only be definitively diagnosed after death, by looking for telltale globs of protein in the brain. Doctors presented with a patient with memory loss, language problems, and other symptoms of Alzheimer’s disease–for which there is no cure–reach a diagnosis by ruling out other causes of dementia, such as stroke. Most of the time they’re right, and their conclusion can later be confirmed by examining the brain after death, but scientists have long been searching for a way of making a definitive diagnosis in a living patient.
Definitively diagnosing Alzheimer’s is a challenge, researchers say, because it’s a complex disease. “We’re understanding more and more of what causes the disorder, but we don’t know for certain,” says David Michelson, vice president of neuroscience at Merck, a pharmaceutical company that is also working on diagnostic biomarkers for Alzheimer’s disease.
Some researchers are using advanced imaging techniques to try to pick up protein accumulations in the brain. Others are looking for biomarkers of the disease in cerebrospinal fluid–obtained with a spinal tap–and in blood.
Satoris’s detection method measures the relative abundance of particular proteins in the blood. Alzheimer’s disease involves inflammation in the brain, and other research has suggested that signs of inflammation “show up in the blood as well,” Buckholtz says.
Plasma contains about 30,000 different proteins, so researchers first narrowed down the field to several hundred signaling proteins. By analyzing 259 blood samples, they identified 18 proteins that are present in distinctive concentrations in the blood of Alzheimer’s patients. This protein signature also distinguishes Alzheimer’s from other causes of dementia, McReynolds says.
Satoris researchers are now working with other collaborators to look for blood biomarkers that could be used to track the progression of the disease. They’re also trying to correlate the diagnostic biomarkers they’ve identified in the blood with those in the cerebrospinal fluid, as well as with the results of brain imaging.
However, until there are better treatments for Alzheimer’s disease, Michelson says that diagnostic tests will be most useful as a research tool because “what’s the use of confirming a diagnosis early if you can’t do anything about it, if you don’t have a treatment that could change what can happen?”
On the other hand, Carrillo says that a definitive diagnosis allows patients and families to plan and prepare for the future, seek out the best care and treatment, and in some cases participate in clinical trials. “That early diagnosis is critical,” she says.