Accumulation of the protein tau in the brain is\u00a0one of the\u00a0hallmarks\u00a0of Alzheimer’s disease. In a paper publishing March 5 in the Cell Press journal\u00a0Cell Press Blue, researchers report a previously unknown mechanism that\u00a0appears to enable\u00a0the build-up of tau. The study, which\u00a0employed\u00a0animal and cellular models as well as patient tissues, suggests a key role for\u00a0tanycytes-specialized brain cells\u00a0that regulate brain-body signaling.\u00a0<\/p>\n
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Our findings reveal a previously underappreciated, disease-relevant role for\u00a0tanycytes\u00a0in neurodegeneration. Focusing on\u00a0tanycyte\u00a0health\u00a0could be\u00a0a\u00a0way\u00a0to improve tau clearance and limit disease progression.”\u00a0<\/p>\n
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Vincent Prevot, corresponding author, INSERM, France<\/p>\n
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Tanycytes\u00a0are a type of non-neuronal brain cell\u00a0that\u00a0are\u00a0primarily\u00a0found in the\u00a0third ventricle of the brain.\u00a0Previous\u00a0research\u00a0has shown that these cells play an active role in shuttling metabolic signals between the\u00a0blood\u00a0and the cerebrospinal fluid\u00a0(CSF)-the liquid that surrounds the brain and spinal\u00a0cord\u00a0and\u00a0acts\u00a0as a communication hub\u00a0for\u00a0maintaining\u00a0homeostasis.\u00a0<\/p>\n
In this study, the researchers\u00a0sought\u00a0to\u00a0better understand how\u00a0tanycytes\u00a0clear toxic molecules such as tau\u00a0to preserve brain health.\u00a0They found\u00a0that the brain cells\u00a0carry toxic molecules out of the CSF and into the blood for disposal,\u00a0and that when they\u00a0don’t\u00a0work properly, tau\u00a0can accumulate\u00a0in the brain.\u00a0<\/p>\n
“Surprisingly, we were\u00a0able to show in\u00a0rodent\u00a0and cellular models\u00a0not\u00a0only\u00a0that\u00a0tanycytes\u00a0were indeed involved in clearing tau\u00a0but also that\u00a0tanycytes\u00a0in the brains of human Alzheimer’s patients\u00a0were fragmented and had changes in gene expression related to this shuttle function,” Prevot says.\u00a0<\/p>\n
The\u00a0team says\u00a0these findings highlight the potential of developing interventions aimed at\u00a0maintaining\u00a0brain homeostasis\u00a0to prevent\u00a0neurodegeneration\u00a0but\u00a0acknowledge several challenges to\u00a0targeting\u00a0tanycytes\u00a0as a way to\u00a0develop interventions for Alzheimer’s. One key limitation is the lack of good animal models for Alzheimer’s disease. Another is the need for\u00a0larger cohorts and\u00a0more\u00a0longitudinal data to\u00a0establish\u00a0causality and define the sequence of events linking\u00a0tanycyte\u00a0dysfunction to\u00a0tau pathology.\u00a0<\/p>\n
“Our findings provide the first evidence for structural\u00a0and functional alterations in these little-known but key brain cells in human disease,” says Prevot.\u00a0<\/p>\n
This work was supported by the European Research Council, National Institutes of Health, the Fondation pour la Recherche\u00a0M\u00e9dicale,\u00a0and the Fondation NRJ for Neuroscience-Institut\u00a0de France.\u00a0<\/p>\n
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