Tanycytes: A New Key Player in Clearing Toxic Tau Proteins from the Brain

A recent study indicates that specialized brain cells called tanycytes play a crucial role in clearing toxic tau proteins from the brain. These proteins are a hallmark of Alzheimer's disease. In individuals with Alzheimer's disease, these cells reportedly malfunction, contributing to the accumulation of tau proteins, a known characteristic of the disease.

Unique Location and Function

Tanycytes, located along the third ventricle of the brain, are unique because they interact directly with both the bloodstream and the cerebrospinal fluid (CSF). This dual contact allows them to bypass the blood–brain barrier, facilitating molecule transport into and out of the brain.

While tanycytes were previously known to transport molecules into the CSF, researchers have now demonstrated that these cells also transport molecules, specifically tau proteins, from the CSF into the bloodstream.

This finding offers a potential explanation for how abnormal tau proteins might accumulate in the brain.

Understanding Tau Proteins and Alzheimer's

Tau proteins typically provide structural support to cells, including brain cells. However, in Alzheimer's disease, these proteins cease to function correctly, becoming 'sticky' and forming clumps that can lead to cell death. These tau tangles predominantly accumulate in brain regions associated with memory.

Experimental Evidence: Tracing Tau Transport

Initial experiments showed tanycytes could transport and release tau in cell cultures. Subsequent experiments provided further insights into this process.

These involved injecting human tau proteins with a fluorescent tag into the CSF of mice. The tau was detected exclusively in tanycytes, which then transported the protein from the CSF into the pituitary gland and subsequently into the bloodstream.

Mice with impaired tanycyte function exhibited increased tau accumulation in the brain and lower levels of tau in the bloodstream, suggesting the importance of tanycytes in tau removal.

Tanycyte Malfunction in Alzheimer's Patients

A comparative analysis of CSF and blood samples from 86 individuals with Alzheimer's and 91 healthy controls revealed reduced tau transfer from CSF to bloodstream in those with the disease, indicating tanycyte malfunction.

Specifically, less of an abnormal tau protein called p-tau181, associated with Alzheimer's, was found in the blood compared to the CSF in affected individuals. Furthermore, postmortem analysis of brain tissue samples showed that tanycytes in people with Alzheimer's disease were fragmented or destroyed compared to those in healthy individuals.