Scientists have found a possible source of brain damage in Alzheimer's disease
Scientists have discovered that the immune process associated with brain damage in Alzheimer's disease can be triggered outside the nervous system. In experiments on mice, dendritic cells in the lymph nodes activated T cells, after which they entered the brain and increased neurodegeneration. About how the immune system can participate in the development of Alzheimer's disease — in the material of Izvestia.
Brain damage can start outside the brain.
Researchers from Washington University School of Medicine in St. Louis studied the role of immune cells in diseases associated with the accumulation of tau protein. The brains of people with Alzheimer's disease and some other neurodegenerative diseases show an increased number of T cells, immune cells that are normally involved in protecting the body.
However, until now it was unclear where they come from and what makes them go to the nervous system. New work has shown that the corresponding signals can be formed outside the brain — in the lymph nodes.
David M. Holtzman, Professor of Neurology at the Barbara Burton and Ruben M. Maurice III University of Washington School of Medicine and senior author of the study
There are many ways to target T cells that have been extensively studied and approved as treatments for other diseases, but many of them have not yet been investigated for neurodegenerative diseases.
The study was published in the journal Nature Neuroscience (NN). The experiments were conducted on mice that developed clusters of tau protein and associated damage to nervous tissue.
T cells receive a signal in the lymph nodes
At the center of the mechanism were two types of immune cells — dendritic cells and T-lymphocytes. Dendritic cells help the immune system recognize molecular targets and transmit information to T cells, which can then attack cells with appropriate signs.
The researchers noticed that the brain itself contains a very small number of cDC1-type dendritic cells. In addition, they practically did not interact with the T cells that appeared after the formation of tau tangles.
This suggested that T-cell activation occurs elsewhere. As a result, scientists have focused on the lymph nodes and other peripheral tissues, where the processes necessary to trigger an immune response can occur.
Scientists have disabled some of the immune cells in mice
To test their hypothesis, the researchers removed dendritic cells from lymph nodes and other tissues in mice that normally developed tau tangles and neurodegeneration. After that, the number of T cells in the brain, especially CD8 T cells, decreased dramatically. At the same time, the associated damage to the nervous tissue decreased.
At the same time, the number of tau tangles in the brain has not changed much. Despite the preservation of these pathological clusters, the mice retained their cognitive abilities. The result indicates that brain damage in the studied model may depend not only on the accumulation of tau protein itself, but also on the subsequent reaction of the immune system.
Tau protein can trigger an immune response
The exact signal that causes dendritic cells to activate T lymphocytes has not yet been established. Scientists suggest that one of the options may be the following chain of events.
Damage to nerve cells associated with tau protein can lead to the release of various substances from the brain. They are able to travel through the lymphatic system to the lymph nodes of the neck. There, dendritic cells can recognize these substances and present them to T cells as a target.
After activation, the T cells are sent back to the brain. Already there, their activity can contribute to further damage to the nervous tissue. For now, this remains a hypothesis that researchers will have to test.
The new mechanism may become a target for treatment
The open pathway is of interest for future research, as its key stages occur outside the brain. This potentially allows them to be affected without having to deliver drugs directly through the blood-brain barrier.
David Holtzman
Until recently, most people, including me, did not think that the immune response was even involved in neurodegenerative diseases caused by the accumulation of protein in the brain. The fact that these dendritic cells are involved in neurodegenerative diseases is very encouraging; we have shown that they are important and that they are a potential target for future therapies.
Now the team of researchers is testing whether it is possible to achieve a protective effect if the activity of dendritic cells is blocked not from birth, as in the original experiment, but in middle age — around the time when tau tangles begin to form. Scientists are also trying to identify a specific signal that directs T cells to the brain.
Переведено сервисом «Яндекс Переводчик»
