An Inserm study reveals a close link between the abnormal accumulation of the Tau protein in the brains of Alzheimer’s patients and the role of tanycytes, cells known to ensure essential exchanges between the brain and the rest of the body. The results published in the journal Cell Press Blue show the involvement of these cells in the transport of the Tau protein and their importance in the pathophysiology of Alzheimer’s disease. Tanycytes could thus be considered as a new therapeutic target
Alzheimer’s disease is manifested by progressive disorders of memory, executive functions as well as temporal and spatial orientation. It is caused by a slow and progressive degeneration of neurons in the hippocampus before spreading throughout the brain.
The diagnosis of Alzheimer’s disease can be based on measuring the presence of a protein in the cerebrospinal fluid (CSF), the Tau protein. In a healthy person, the presence of Tau in the CSF is low: it is secreted there by neurons then eliminated into the blood. But, in people with the disease, the structure of Tau changes and can no longer fulfill its normal role inside neurons. It accumulates there in a pathological form, which disrupts the functioning of the brain. This accumulation gradually leads to the degeneration and death of neurons, causing cognitive decline.
The mechanisms leading to pathological accumulation of Tau protein are not fully understood and are an active area of research.
For more than 20 years, Vincent Prévot, Inserm research director and his team at the Lille Neuroscience & Cognition research center (Inserm/University of Lille/Lille University Hospital), have been studying the specific role of certain cells called tanycytes. These are known to ensure essential exchanges between the brain and the rest of the body, in particular between the blood system and the cerebrospinal fluid. For example, they detect and transport leptin (the satiety hormone) to the brain, and it is thanks to their function that the brain regulates appetite and energy balance.
In a new study, the team for the first time investigated the potential role of these cells in the pathological context of Alzheimer’s disease. She methodically followed several steps.
The researchers first validated that tanycytes were indeed involved in the transport of Tau. To do this, they injected the Tau protein into the cerebrospinal fluid and observed its path using fluorescence techniques. This first experiment allowed them to visualize how Tau was captured in the cerebrospinal fluid by the tanycytes and then transported in their extension to the blood capillaries.
From this observation, they hypothesized that tanycytes capture Tau then release it and then eliminate it in the blood.
To verify this second idea, the researchers studied the consequences of blocking the transport of tanycytes, by genetically expressing in the cells the botulinum toxin which prevents them from functioning. Results: They observed a loss of Tau evacuation from the CSF into the blood.
The researchers thus showed for the first time in animals that tanycytes were the main route of transport of Tau proteins from the brain to the blood circulation.
In parallel, and this time on mouse models presenting a high level of Tau in the CSF, they also showed that by blocking the activity of tanycytes, these mice developed the symptoms of dementia characteristic of Alzheimer’s disease earlier, and more generally a tauopathy, a disease characterized by an accumulation of abnormal forms of the Tau protein.
To go further, researchers studied the brains of people who died with Alzheimer’s. These analyzes confirmed the presence of Tau proteins in tanycytes, as had been shown in animals. They also noticed that the tanycytes were damaged: their extensions were fragmented, thus interrupting the communication pathway between the CSF and the blood. This alteration seems specific to Alzheimer’s disease – researchers have not found it in the brains of patients suffering from other types of dementia.
“Our results show in an unprecedented way the capacity of tanycytes to transport the Tau protein from the cerebrospinal fluid to the blood and the importance of these cells in the pathophysiology of Alzheimer’s disease. They suggest that the degradation of these cells contributes to Alzheimer’s disease. explains Vincent Prévot.
“Tanycytes could thus be considered as a new therapeutic target. What if the good health of these cells could ultimately prevent the development of the disease? “, concludes the researcher.
Inserm press release, March 5, 2026
