Researchers saw how the Tau protein leads to Alzheimer’s progression in the brain and is now closer to a cure

By 2020, 5.8 million Americans suffered from Alzheimer’s. According to the CDC, that number is expected to rise to 14 million by 2060. A cure for these people has long been elusive, but that may change faster than we think thanks to a new study illustrating how Alzheimer’s-associated proteins accumulate in the brain. The results, published on Friday in The progress of science, arms researchers with new insights into how the disease progresses and can lead to new ideas for more effective treatments.

Alzheimer’s is a disease defined by proteins that do not behave badly, according to Tuomas Knowles, a researcher at the University of Cambridge and co-author of the new study. One of these proteins is called tau. In Alzheimer’s disease, ropes begin to misbehave and form clumps inside the brain cells, disrupting their ability to communicate with each other.

Reducing the accumulation of these lumps of tau may be a way to fight Alzheimer’s disease, but researchers must first find out how the accumulation occurs.

Knowles told The Daily Beast that there are two main processes underway in the silent takeover of the brain. One process involves lumps of tau that spread from one part of the brain to another. The second process involves tau replication – the clumps grow and multiply in place.

A disease can only move as fast as its slowest step allows (also called the “speed-limiting” step), so Alzheimer’s researchers are deeply interested in finding out which of these processes control silent progression through the brain. more slowly. “If you want to intervene therapeutically, you have a lot more effect if you choose the speed-limiting step,” Knowles said. “If you choose a step that is not rate-limiting, you actually risk not having any kind of advantage.”

Much research has focused on how to stop the lumps of tau from spreading, but according to the new study, this may not be an effective way to treat the disease. Using five different sets of brain data in people with Alzheimer’s, the researchers found that in the middle and later stages of the disease, tau replication was actually a much more important factor than tau spread.

Brian Kraemer, a professor at the University of Washington who was not involved in the study, told The Daily Beast that the approach used in this study “is a new idea for the field. I think it could tell us some important things that we do not really understand well about how tauopathies [neurodegenerative diseases involving tau] progress. I thought it was pretty cool. “

For the first time, researchers were also able to determine an average for how fast this replication occurs in humans. Using data from post-mortem brain tissue as well as brain scans from living Alzheimer’s patients, the researchers found that the average replication time is about five years. This velocity is orders of magnitude slower than the velocity observed in test tube and mouse experiments. In a field that has often struggled to translate research from animals to humans – dozens of drugs have reversed Alzheimer’s symptoms in mice while no one has been able to achieve this in humans – this discovery underscored the importance of studying disease processes in actual patients.

The slow rope replication rate in humans is also good news in itself. “What it tells us is that the environment in the brain has evolved almost completely keep this process under control, ”said Knowles.

“I like to be optimistic about these things,” he said. “In fact, you do not have to do much with this number until you have actually cured the disease. [The doubling time] does not have to go to a million years … You just have to slow it down maybe by a factor of two to three. And then it’s just so slow that it’s not a problem in our lifetime. ”

The next step for researchers will be to find drug candidates, molecules that can modulate this rate of replication and potentially slow the disease down to a point where a patient’s cognitive function is hardly impaired.

Kraemer added that the methods used in this study could also provide interesting insights into other debilitating neurodegenerative diseases that also involve abnormal tau proteins. This includes argyrophilic corneal disease (a relatively common form of dementia); and chronic traumatic encephalopathy (CTE), which is seen in football players and others who have suffered repeated head injuries.

Knowles looks forward to future research using tools at the molecular level to answer larger questions about neurodegenerative diseases. “We are really keen to bring our insights and tools as chemists where we can actually deal with phenomena at the molecular level,” he said. “But now actually being able to do this in the right person, with the right patient data. I think it’s incredibly exciting.”


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