Washington University researchers are one step closer to a blood-based test to screen for Alzheimer’s disease after developing a technique that allows them to detect tiny amounts of a protein linked to the disease in blood plasma.
In a study published Tuesday in the Journal of Experimental Medicine, scientists found that levels of the p-tau-217 protein are elevated during early stages of the disease and could lead to a simple blood test — instead of an invasive spinal tap or expensive medical scan — capable of diagnosing the neurodegenerative disorder up to two decades before any symptoms appear.
“Using plasma is much more convenient at the clinical side than testing cerebrospinal fluid, much less invasive, easier to get, and allows us to think about doing screening on a large population,” said Washington U. neurology instructor Nicolas Barthélemy, lead author of the study. “If we can use this biomarker for predicting Alzheimer’s disease pathology, it’s a huge improvement for future tests and clinical trials.”
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Alzheimer’s disease causes a normally occurring protein called amyloid-beta to clump together in the brain and form plaques that collect between neurons and disrupt their ability to function. And the tau protein, which researchers examined in this study, aggregates and causes tangles in the neurons of Alzheimer’s patients.
Amyloid-beta and tau begin changing years before any cognitive symptoms, such as memory loss and confusion, become apparent, but currently the only way to detect the onset of the disease involves either a positron emission tomography or PET scan to visualize the brain, or a spinal tap to measure changing protein levels in the cerebrospinal fluid, the liquid that surrounds the spinal cord and brain.
Barthélemy developed a method that uses mass spectrometry, which calculates the mass of different molecules in a sample, to measure the amount of p-tau-217 in as little as 4 milliliters of blood, which is less than is typically drawn for blood tests.
Researchers were looking for a needle in a haystack — these blood samples contained less than a trillionth of a gram of the protein.
P-tau-217 is just one of many biomarkers that can be used to track the progression of Alzheimer’s disease. Researchers envision a future in which these biomarkers will be combined in a single blood test panel that will allow clinicians to more accurately diagnose their patients.
Washington U. neurology professor Dr. Randall Bateman, senior author of the study, said that the tests would accelerate the search for new treatments by making it faster and cheaper to screen participants for research.
“These tests open up our ability to do trials not of 1,000 or 2,000 but trials of 10,000, even 50,000 people,” he said. “It allows the research community to do all kinds of studies that were unimaginable before and that’s going to revolutionize how fast we move toward effective treatments and prevention of Alzheimer’s.”
The new tests will also allow researchers to use blood stored in a biobank from decades ago to review patients who had abnormal tau protein levels and see how they are faring today to better understand the progression of the disease.
Alzheimer’s diagnoses are now made with the help of cognitive tests and clinical interviews with patients’ caregivers and family. But a blood test will help clinicians rule out other conditions — other dementias, stroke, tumors, hydrocephalus, thyroid issues, depression, anxiety and even normal aging — that may also involve cognitive impairment.
Before the tests can be used clinically, researchers hope to lower the blood volume drawn to run the analyses, making it easier to conduct long-term studies. They will also need to verify the tests’ reliability and seek regulatory approval.
Still, such a test could come with an ethical dilemma: There’s no known cure for Alzheimer’s, and only four FDA-approved drugs to treat symptoms. So the test could inform patients of a disease whose onset they can’t predict and whose progress they are powerless to stop.