New Blood Test Could be "Game Changer" for Alzheimer's Drug Development

Aug 11, 2019

Beta amyloid plaques (brown) in the brain are strongly linked to Alzheimer's disease. A new blood test is a sensitive, early indicator of such brain changes.
Credit National Institute on Aging, NIH / Public Domain

Alzheimer's disease affects at least five and a half million people in the United States. One of the greatest challenges in trying to treat the disease is catching it early enough. There's currently no reliable way to diagnose Alzheimer's until symptoms like memory loss are already recognizable. And by that time the brain has suffered years if not decades worth of damage. That's likely why many promising drug trials in recent years have failed.

But a test capable of diagnosing Alzheimer's years before there are any symptoms may be on the horizon. Researchers from Washington University School of Medicine in St. Louis say they can use a combination of a blood test, a genetic test, and a patient's age to predict with 94 percent accuracy whether or not a person will develop brain changes that are linked to Alzheimer's disease.

The blood test compares the levels of two versions of the amyloid beta protein, one of two main proteins involved in the Alzheimer’s pathology.

“We look at one form that's 40 amino acids long, and one that's slightly longer - 42 amino acids,” explained Suzanne Schindler, an assistant professor of neurology at Washington University in St. Louis and lead author on that new study. “What we found is that the ratio of those two proteins is very accurate in predicting whether someone has early Alzheimer's disease brain changes.”

By “very accurate,” Schindler means roughly 88 percent accurate. To get to 94 percent accuracy, Schindler and her colleagues added in other criteria – a genetic mutation known as ApoE e4, and age.

Schindler says this test is even more sensitive to early brain changes than the current gold standard, a specialized brain scan known as amyloid PET.

That doesn’t mean it’s testing for Alzheimer’s disease, itself. Some people do develop amyloid plaques and never get dementia.

“This test is really for the amyloid brain changes, not for clinical symptoms of Alzheimer's disease,” Schindler emphasized.

Still, Schindler says the test could be used within a year or two to screen candidates for Alzheimer’s drug trials. In fact, she says it could be a “game changer.”

“We think that by using this blood test, that we could recruit people much more quickly and much faster, and that would really translate to Alzheimer's disease drug trials being cheaper and faster,” she said. “And hopefully that will mean that we can find a drug that works.”

In fact, Schindler says it’s quite possible that drugs that have failed in previous clinical trials might work if given to patients diagnosed earlier with a blood test, like hers.

“A lot of the drug trials that have been done so far have used patients who have significant symptoms and are pretty far along in the course of the disease,” she explained. “It's much harder to reverse the disease than to prevent it. So, we really need to find a way to figure out who's at risk and enroll them in studies before they even have symptoms.”

As a clinician, as well as a researcher, Schindler says this test could make a big difference for patients whose dementia doesn’t have a clear-cut cause. Confirming (or refuting) the presence of early amyloid brain changes could guide patients’ and doctors’ decisions about which treatments to pursue.

Eventually, Schindler would like to see a test for amyloid brain changes become as widespread and routine as cholesterol testing. But she says it’s too soon for that.

“We don't have effective treatments right now,” Schindler said. “So, if we test someone and they're positive, and they don't have clinical symptoms, there's not necessarily a lot they can do about it.”

Which brings things full circle to accelerating the development and testing of Alzheimer’s drugs, which Schindler says is the top priority with this new test.