L’ESSENTIEL
- For the first time, scientists have shown that tanycytes – brain cells – participate in the transport of tau protein out of the brain.
- Their dysfunction could cause the accumulation of tau, which contributes to neuron degeneration and the progression of Alzheimer’s disease.
- Damaged tanycytes in the brains of Alzheimer’s patients “could thus be considered a new therapeutic target.”
Alzheimer’s disease, characterized by the slow and progressive degeneration of neurons in the hippocampus before spreading throughout the brain, involves the buildup of pathological tau protein in the brain and cerebrospinal fluid (CSF) instead of its normal elimination into the blood. “However, the underlying mechanisms remain obscure,” according to researchers from Inserm, the University of Lille, and the Lille University Hospital (United States). To address this, the team conducted a study, published in Cell Press Blue, focusing on tanycytes, cells known to facilitate essential exchanges between the brain and the rest of the body, particularly between the bloodstream and the CSF. “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.”
Tanycytes Capture Tau Protein and Transport it to Blood Vessels for Elimination
To determine the potential role of tanycytes in the context of Alzheimer’s disease, the team used animal and cell models, as well as tissue from patients. They injected tau protein into the CSF and observed its path using fluorescence techniques. For the first time, the authors found that, in mice, tanycytes were the primary route for evacuating tau proteins from the brain into the bloodstream. They then demonstrated that, in mice with high levels of tau in the CSF, blocking tanycyte activity promoted tauopathy (a disease characterized by the accumulation of abnormal forms of tau protein) and the early development of dementia symptoms characteristic of Alzheimer’s disease.
Alzheimer’s: Tanycytes are Damaged in Patients
In people who have died with Alzheimer’s disease, the plasma and CSF ratios of total tau protein and tau p181 protein are reduced. Specifically, tanycytes in patients exhibit highly fragmented extensions and significant transcriptomic alterations. In simpler terms, the cells are damaged, which explains the elimination deficit. “This alteration appears specific to Alzheimer’s disease – the researchers did not find it in the brains of patients with other types of dementia,” according to an Inserm press release.
Understanding how the brain clears harmful proteins like tau is a critical step in developing effective treatments for Alzheimer’s disease, a condition that currently affects millions worldwide.
“A New Therapeutic Target”
“Our results show, for the first time, the ability of tanycytes to transport tau protein from the CSF 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. (…) Tanycytes could thus be considered a new therapeutic target. And if the good health of these cells could ultimately prevent the development of the disease?” said Vincent Prévot, Inserm research director who led the study.
