New method to measure tau protein levels in the blood

New method to measure tau protein levels in the blood

Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes. The tau proteins are the product of alternative splicing from a single gene that in humans is designated MAPT (microtubule-associated protein tau) and is located on chromosome 17.

Brain protein tau plays a role in neurodegenerative diseases such as Alzheimer’s and many other neurodegenerative diseases, including chronic traumatic encephalopathy, which torments professional boxers and football players. Tau-based diseases can lead to memory loss, confusion and, in some, aggressive behavior. But there is no easy way to determine whether people's symptoms are linked to tau tangles in their brains.

However, a team led by scientists at Washington University School of Medicine in St. Louis has found a way to measure tau levels in the blood. The research was published in Science Translational Medicine. The study, in mice and a small group of people, could be the first step toward a noninvasive test for tau.

"We showed that you can measure tau in the blood, and it provides insight into the status of tau in the fluid surrounding cells in brain," said senior author David Holtzman. "People with tau diseases have a wide range of symptoms because basically, wherever tau is aggregating, those parts of the brain are degenerating," Holtzman said. "So if it's in a memory area, you get memory problems. If it's in a motor area, you get problems with movement."

Generally, a blood-based screening test, likely years away, would be a relatively easy way to identify people whose symptoms may be due to problems with tau, without subjecting them to potentially invasive, expensive or complicated tests. Holtzman explained that there is no test that accurately reflects the status of tau in the brain that is quick and easy for patients. Some brain scans can measure tau tangles, but they are not approved for use with patients yet. Tau levels can be measured in the cerebrospinal fluid that surrounds the brain and spinal cord, but in order to get to that fluid, you have to do a spinal tap, which is invasive.

In the brain, most tau proteins are inside cells, some are in tangles, and the remainder float in the fluid between cells. Such fluid constantly is being washed out of the brain into the blood, and tau comes with it. However, the protein is cleared from the blood almost as soon as it gets there, so the levels, while detectable, typically remain very low. So the scientists assumed if they could keep tau in the blood longer, the protein would accumulate to measurable levels. Allowing the protein to accumulate before measuring its levels would magnify.

At last, the researchers injected a known amount of tau protein directly into the veins of mice and monitored how quickly the protein disappeared from the blood. The researchers showed that half the protein normally disappears in less than nine minutes. When they added an antibody that binds to tau, the half-life of tau was extended to 24 hours. And that’s definitely a good news.

To determine whether the antibody could amplify tau levels in an animal's blood high enough to be measured easily, they injected the antibody into mice. Within two days, tau levels in the mice's blood went up into the easily detectable range. The antibody acted like a magnifying glass, amplifying tau levels so that differences between individuals could be seen more easily.

Tau levels in people's blood also rose dramatically in the presence of the antibody. The researchers administered the antibody to four people with a tau disease known as progressive supranuclear palsy. Their blood levels of tau rose 50- to 100-fold within 48 hours.

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