French researchers have made a significant advancement in understanding Alzheimer’s disease with the discovery of a specific type of brain cell’s role in the disease’s development.
A recent study conducted by researchers from the French National Institute of Health and Medical Research (Inserm), the University of Lille, and Lille University Hospital indicates that a dysfunction in these cells may be a key factor in the abnormal accumulation of the Tau protein in the brain – a prominent biological marker associated with the disease, according to the Inserm website.
Alzheimer’s disease is one of the most prevalent neurodegenerative disorders worldwide, characterized by progressive disturbances in memory and cognitive abilities, such as impaired decision-making, thinking, and temporal and spatial orientation. This discovery offers a novel avenue for potential therapeutic interventions in a disease that currently has limited treatment options.
The disease occurs due to the gradual degeneration of neurons in the hippocampus, the area of the brain responsible for memory, before progressively spreading to other parts of the brain.
A key biological sign of the disease is the abnormal accumulation of Tau protein inside neurons, a protein that plays an significant role in maintaining the internal structure of these cells.
What happens to the “Tau” protein in a healthy state?
In a healthy brain, neurons produce Tau protein in limited quantities, which is then secreted into the cerebrospinal fluid (the fluid surrounding the brain and spinal cord). It is then gradually eliminated through transfer into the bloodstream.
However, in individuals with Alzheimer’s disease, the structure of this protein changes, rendering it unable to perform its normal function, and it begins to accumulate inside neurons pathologically.
Over time, this accumulation disrupts neuronal function and ultimately leads to cell death, causing cognitive decline and memory loss.
The new study focused on a type of brain cell called “Tanycytes,” located near the brain ventricles, and playing a role in regulating the exchange between blood and cerebrospinal fluid.
The research team, led by Vincent Prévot, had been studying these cells for over twenty years, discovering they are responsible for transporting certain important hormones, such as leptin, which controls appetite and energy balance in the body.
However, the new study revealed for the first time that these cells have a direct role in transporting Tau protein from the brain to the blood.
How did scientists reach this discovery?
Researchers relied on a series of precise experiments. They initially injected Tau protein into the cerebrospinal fluid of animal models, then tracked its path using fluorescence-based imaging techniques.
The results showed that Tanycytes capture Tau protein from the cerebrospinal fluid and then transport it through their cellular extensions to the capillaries, where it is eliminated into the bloodstream.
Based on these results, researchers hypothesized that these cells form the main pathway for removing Tau protein from the brain.
To test this hypothesis, the researchers disabled the function of the Tanycytes using genetic modification that allows the production of botulinum toxin inside these cells, preventing them from performing their function.
The results showed that disabling these cells stopped the transfer of Tau protein from the cerebrospinal fluid to the blood, causing it to accumulate inside the brain.
Scientists too observed that mice with disabled cells showed symptoms of dementia earlier compared to others.
To confirm the results, the researchers also studied the brains of people who died from Alzheimer’s disease.
Analyses revealed the presence of Tau protein inside the Tanycytes in patients, and scientists noted that these cells were clearly damaged. Their cellular extensions were fragmented and broken, disrupting the normal pathway that allows the protein to move from the cerebrospinal fluid to the blood.
Interestingly, this damage was not observed in the brains of patients suffering from other types of dementia, suggesting it may be specific to Alzheimer’s disease.
Researchers believe this discovery may open new avenues for developing treatments for Alzheimer’s disease. If the health of Tanycytes is proven to play a key role in preventing the accumulation of Tau protein, these cells could become a new therapeutic target. The findings highlight the complex interplay of cellular mechanisms in the development of Alzheimer’s disease.
