Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration

• DOI: 10.1084/jem.20211275
• Publication Date: 2022-02-25T14:22:06Z
• Authors: Kazuhisa Ishida; Kaoru Yamada; Risa Nishiyama; Tadafumi Hashimoto; Itaru Nishida; Yoichiro Abe; Masato Yasui; Takeshi Iwatsubo
• Keywords: Glymphatic System; Tau protein; Tauopathy

Accumulation of tau has been implicated in various neurodegenerative diseases termed tauopathies. Tau is a microtubule-associated protein but also actively released into the extracellular fluids including brain interstitial fluid and cerebrospinal (CSF). However, it remains elusive whether clearance impacts tau-associated neurodegeneration. Here, we show that aquaporin-4 (AQP4), major driver glymphatic system, facilitates elimination from to CSF subsequently deep cervical lymph nodes. Strikingly, deletion AQP4 not only elevated markedly exacerbated phosphorylated deposition associated neurodegeneration brains transgenic mice expressing P301S mutant tau. The current study identified pathway central nervous suggesting novel regulatory mechanism whose impairment contributes aggregation