Studying age-related diseases gives researchers a better understanding of the risk factors that affect people in later life. By focusing on heart disease, Alzheimer’s and obesity — conditions that have major quality-of-life implications for ageing populations — these three early career researchers are bringing fresh perspectives to a fast-moving field.
THOMAS KARIKARI: Targeting tau
Thomas Karikari wants to develop more accessible blood tests for Alzheimer’s disease.Credit: Tom Altany/University of Pittsburgh
Two key hallmarks of Alzheimer’s disease are tangles of tau proteins that form inside neurons and amyloid plaques that build up between the neurons. Brain scans and spinal taps are useful for detecting these abnormalities, but Thomas Karikari wants to give patients a less invasive option: a simple blood test.
“We need to find the best ways of understanding and identifying individuals who may be at risk,” says Karikari, a neuroscientist at the University of Pittsburgh in Pennsylvania. A blood test, he says, “can provide a snapshot of what’s happening in the brain, even up to 20 years before symptoms manifest”.
Early in Karikari’s career, the general consensus around blood-based tests was one of incredulity, he says. “Everyone just went: ‘No, no, no, we don’t talk about it because they’re too difficult to do’.” So, as a postdoctoral student at the University of Gothenburg in Sweden, he set himself the challenge of designing a blood test that can detect a form of tau called p-tau181, which exists in high levels in the brains of people who have Alzheimer’s and accumulates as the disease progresses.
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After screening dozens of antibodies, Karikari and his collaborators had a lightbulb moment: the part of the tau protein that is commonly detected in blood is the left end section — not the middle part that spinal-fluid tests usually target. This insight helped them to design antibodies that could bind to the left portion of the tau protein in a blood sample. The discovery was like “cracking the code”, says Karikari, and the team went on to develop a blood test1 that detects p-tau181 with an accuracy of more than 82%.
Since then, Karikari has developed numerous other blood tests for Alzheimer’s disease, including two that can detect p-tau217, another blood biomarker for Alzheimer’s disease2.
Alzheimer’s blood tests have limitations, which has curbed their widespread use. For one thing, labs use different methods to measure the same protein, which means the results aren’t always consistent. And the fact that tau doesn’t just appear in the brain, but is also common in the liver, kidney, heart and other organs of a healthy person means “we might run into some false positivity” when it’s detected in the blood, says Karikari. One of the blood tests that his team has developed specifically targets brain-derived tau3.
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