Scientists Discover Hidden Brain Cells That Could Stop the Accumulation of Tau Proteins in Alzheimer’s Disease

The accumulation of tau protein in the brain is a characteristic feature of Alzheimer’s disease. In a study published in the journal Cell Press Blue, researchers describe a newly identified biological process that could shed light on how tau accumulation occurs.

The research combined animal experiments, cell studies, and analyses of patient tissue. The results point to an important role for tanycytes, specialized brain cells that regulate communication between the brain and the rest of the body. “Our findings reveal a previously underestimated, disease-relevant role for tanycytes in neurodegeneration,” says corresponding author Vincent Prevot of INSERM in France. “Focusing on tanycyte health could be a way to improve tau clearance and limit disease progression.”

What are Tanycytes?

Tanycytes are non-neuronal brain cells found mainly in the third ventricle of the brain. Previous studies have shown that they help transmit metabolic signals between the bloodstream and cerebrospinal fluid (CSF). This fluid surrounds the brain and spinal cord and acts as a communication network that helps maintain the body’s internal balance.

The third ventricle is a cavity filled with cerebrospinal fluid (CSF) in the center of the brain that is part of the ventricular system. Among other things, this system serves to produce and transport CSF and protect the brain. Tanycytes are found in the lining of this ventricle and form a special type of ependymal cell that is notable for its elongated structure. They have long cell processes that extend from the surface of the ventricle deep into the surrounding brain tissue, particularly the hypothalamus.

The hypothalamus is a central hub for many vital regulatory processes in the body, including hunger and satiety, energy balance, body temperature, hormone control, and circadian rhythms. Tanycytes play an important mediating role in this area, as they act as an interface between the bloodstream, cerebrospinal fluid, and the nerve cells of the hypothalamus. Using special transport mechanisms, they can absorb various metabolic signals, such as hormones, nutrients, or other chemical messengers, from the blood and transmit them to the brain. In this way, they help to ensure that the brain continuously receives information about the current state of the body, for example, about energy requirements or blood glucose levels.

An important aspect of their function is that tanycytes regulate communication between the peripheral body and the central nervous system. They act as sensors and mediators, so to speak: on the one hand, they register changes in the blood, and on the other hand, they pass on this information via the cerebrospinal fluid or through direct contact with nerve cells. The cerebrospinal fluid surrounding the brain and spinal cord not only serves as mechanical protection, but also as a transport medium for signal molecules. This network allows information to be distributed relatively quickly throughout the central nervous system.

Furthermore, recent research suggests that tanycytes may also be involved in the formation of new nerve cells. Some studies suggest that certain subtypes of these cells possess properties of stem cells and can produce new neuronal or glial cells under certain conditions. This ability could be particularly important in the hypothalamus, enabling adaptations to long-term changes in metabolism or energy balance.

How Tanycytes Help Remove Toxic Tau

Tanycytes may play a previously underestimated role in protecting the brain from neurodegenerative diseases, particularly in relation to the removal of the tau protein. Tau is a protein that normally occurs in nerve cells, where it supports the stability of microtubules. These microtubules form a kind of transport system within the cells and are important for the transmission of nutrients and signals. Under certain conditions, however, tau can change its normal structure, misfold, and aggregate into toxic aggregates. Such accumulations are a characteristic feature of Alzheimer’s disease and are closely related to the progressive loss of nerve cells and cognitive functions.

In the new study, the scientists investigated how tanycytes help eliminate harmful molecules such as tau, thereby supporting brain health. Their findings show that these cells transport toxic substances from the CSF into the bloodstream, where they can be excreted from the body. If this transport system does not function properly, tau can accumulate in the brain. “Surprisingly, in rodent and cell models, we were able to show not only that tanycytes are indeed involved in tau clearance, but also that tanycytes in the brains of Alzheimer’s patients were fragmented and showed changes in gene expression related to this shuttle function,” Prevot said.

Since CSF acts as a transport medium for various molecules in the brain, it also represents a possible pathway for removing toxic substances from the brain. The researchers were able to show that tanycytes take up tau molecules from the CSF and then transport them toward blood vessels via their long cell extensions. From there, the molecules enter the bloodstream, where they can ultimately be removed via the body’s normal detoxification and excretion mechanisms.

Cleansing Mechanism Disrupted in Alzheimer’s Patients

In this process, tanycytes act as a kind of “shuttle system” or transport bridge between the cerebrospinal fluid and the blood. They recognize certain molecules, actively absorb them, and transport them through their cell structure. This mechanism is particularly important because the brain is strongly protected by the blood-brain barrier. Although this barrier prevents many harmful substances from entering the brain from the blood, it also makes it difficult to remove waste products from the brain tissue. Tanycytes could therefore represent an important alternative route for the disposal of such metabolic products.

The results of the study also show that this cleansing mechanism may be disrupted in Alzheimer’s patients. In examinations of brain tissue, the researchers found that tanycytes in people with Alzheimer’s disease exhibit structural changes. Many of these cells were fragmented, i.e., partially broken or damaged, and showed changes in gene expression related to their transport function. Such changes could prevent the cells from efficiently performing their task as a transport and disposal system. If toxic tau is not sufficiently removed from the cerebrospinal fluid, it can accumulate in the brain and promote the formation of so-called neurofibrillary tangles – one of the most important pathological hallmarks of Alzheimer’s disease.

Possible Implications for the Treatment of Alzheimer’s

These findings are particularly relevant because they provide a new understanding of how the brain normally removes harmful proteins and why this process can fail in neurodegenerative diseases. While many previous Alzheimer’s studies have focused primarily on nerve cells or the well-known amyloid plaques, this research is also bringing non-neuronal cells such as tanycytes into sharper focus. If the function of these cells could be stabilized or improved, this could open up new therapeutic approaches in the long term. For example, future treatments could aim to increase the transport capacity of tanycytes or repair the cellular mechanisms that are disrupted in Alzheimer’s disease.

The researchers say their findings suggest that protecting the brain’s internal balance could help slow neurodegeneration. At the same time, they caution that developing therapies that target tanycytes will require overcoming several challenges.

One obstacle is the lack of reliable animal models that fully replicate Alzheimer’s disease. Another challenge is the need for larger patient groups and long-term studies to determine cause and effect and clarify how tanycyte dysfunction can lead to tau accumulation. “Our findings provide the first evidence of structural and functional changes in these little-known but important brain cells in human disease,” says Prevot.