TMC PULSE

t m c n e w s . o r g 28 Detecting Alzheimer's Before Symptoms Arise A new blood test boasts more than 90 percent accuracy when combined with other risk factors W hen it comes to break- throughs in research on Alzheimer's disease—a debilitating and progressive neurological disor- der that will affect an estimated 14 million Americans by 2060— scientists are focused on three pillars: prevention, early detection and treatment. But Alzheimer's is notoriously complex, and answers about the nature of the condition and how to best treat it remain elusive. Still, there is progress, and recent research conducted at Washington University School of Medicine in Missouri may advance the mission for early detection through a surprisingly simple technique: a blood test. "It's really exciting," said Suzanne Schindler, M.D., Ph.D., assistant professor of neurology at the Knight Alzheimer Disease Research Center at Washington University School of Medicine and lead author of the study. "I think it really has the potential to speed up finding drugs that work." The research, published in the journal Neurology, claims that by measuring levels of amyloid beta protein in the bloodstream, researchers could estimate whether there is a buildup of that protein in the brain—a hallmark of Alzheimer's disease. Combined with two other risk factors, including age and the presence of the APOE4 gene, a genetic variant that has been asso- ciated with developing Alzheimer's disease, the amyloid blood test is up to 94 percent accurate, the research- ers concluded. The blood test employs a tech- nique known as mass spectrometry to measure two forms of amyloid beta in the bloodstream, amyloid beta 42 (Aβ42) and amyloid beta 40 (Aβ40). According to Schindler, Aβ42—the longer of the two, com- prised of 42 amino acids rather than 40—is "stickier" and much more likely to accumulate in the brain when plaques are present. Every person makes both forms, Schindler explained, and while the amount of Aβ42 and Aβ40 varies from person to person, the ratio of their quanti- ties does not—unless an individual has developed plaques in their brain. "We know that most of the amy- loid that is deposited in the brain, in the plaques, is the longer form—the Aβ42. And we have long known that … as amyloid accumulates in the brain, Aβ42 goes down in the cerebral spinal fluid, which is kind of the opposite of what you'd think. Usually when something goes up in the brain, you'd expect it to go up in the fluid that is around the brain," she said. In this case, however, Schindler said it is likely that the plaques are clinging to the Aβ42, so the A PET scan from Georgetown University Hospital in Washington, D.C., shows results from a study on Alzheimer's disease and biological changes in the brain. B y A l e x a n d r a B e c k e r Credit: AP Photo/Evan Vucci, File ratio changes in the bloodstream: Aβ42 goes down because it is getting stuck in the brain, and Aβ40 remains more or less constant. "When that ratio gets low, there's very, very commonly a reason for it, which is the plaques," Schindler said. Since the study's publication, the researchers have further validated their results and are working on optimizing and scaling the test. One of the study's co-authors, Randall J. Bateman, M.D., the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine, was awarded a grant to pursue a clinical trial to further test the accuracy of the process. Notably, Bateman co-founded a company with another colleague and co-au- thor, David M. Holtzman, M.D., chair of neurology and scientific director of the Hope Center for Neurological Disorders at Washington University School of Medicine, that has been granted breakthrough device status from the U.S. Food and Drug Administration to commercialize the test. A cheaper, easier test The test is still a long way from regular use in a doctor's office, but if it does find its way into the clinic, it could revolutionize current methods for early detection of Alzheimer's. "It would be a lot easier if, instead of having to use a PET scan—which is expensive—we could simply measure something in the blood and have the same amount of certainty as we do with the PET scan," said Joseph Masdeu, M.D., Ph.D., director of the Nantz National Alzheimer Center at Houston Methodist, which was not involved in this particular study. Today, physicians utilize the pos- itron emission tomography (PET) scan, which uses a radioactive tracer to reveal detailed images of tissues and organs, to detect abnormalities in the brain, including presence of the amyloid beta plaques or abnormal levels of tau protein— another marker for Alzheimer's. But as Masdeu pointed out, a cheaper, easier test—with just as much accu- racy—could lead to earlier detection in more patients. "This will help propel the field, certainly, because any time you can do something less expensively, you

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