Glymphatic clearance of extracellular tau and its pathological implications

Kazuhisa Ishida, Kaoru Yamada

Department of Neuropathology, Graduate School of Medicine, The University of Tokyo

How metabolites produced in ISF are ultimately cleared from brain has remained as a persistent question for decades.　Recent discovery of glymphatic system and meningeal lymphatic drainage is a breakthrough in the field;however, how these pathways are involved in clearance of proteins found in neurodegenerative disorders, especially proteins that normally resides inside of neurons but its extracellular presence is relevant to disease progression, remained elusive.　Recently we have discovered extracellular tau is cleared by the glymphatic system and its impairment markedly increased tau aggregation and neurodegeneration.　In this review article, we introduce our findings along with recent advances in the field and also discuss the possible future prospects.

Address correspondence to Dr. Kaoru Yamada, Department of Neuropathology, Graduate School of Medicine, The University of Tokyo (7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan)