Accumulation of the protein tau in the brain is one of the hallmarks of Alzheimer's disease. In a paper publishing March 5 in the Cell Press journal Cell Press Blue, researchers report a previously unknown mechanism that appears to enable the build-up of tau. The study, which employed animal and cellular models as well as patient tissues, suggests a key role for tanycytes—specialized brain cells that regulate brain-body signaling.
"Our findings reveal a previously underappreciated, 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."
Tanycytes are a type of non-neuronal brain cell that are primarily found in the third ventricle of the brain. Previous research has shown that these cells play an active role in shuttling metabolic signals between the blood and the cerebrospinal fluid (CSF)—the liquid that surrounds the brain and spinal cord and acts as a communication hub for maintaining homeostasis.
In this study, the researchers sought to better understand how tanycytes clear toxic molecules such as tau to preserve brain health. They found that the brain cells carry toxic molecules out of the CSF and into the blood for disposal, and that when they don't work properly, tau can accumulate in the brain.
"Surprisingly, we were able to show in rodent and cellular models not only that tanycytes were indeed involved in clearing tau but also that tanycytes in the brains of human Alzheimer's patients were fragmented and had changes in gene expression related to this shuttle function," Prevot says.
The team says these findings highlight the potential of developing interventions aimed at maintaining brain homeostasis to prevent neurodegeneration but acknowledge several challenges to targeting tanycytes as a way to develop interventions for Alzheimer's. One key limitation is the lack of good animal models for Alzheimer's disease. Another is the need for larger cohorts and more longitudinal data to establish causality and define the sequence of events linking tanycyte dysfunction to tau pathology.
"Our findings provide the first evidence for structural and functional alterations in these little-known but key brain cells in human disease," says Prevot.
