Here we study the glymphatic system using MRI, the clearance of parenchymal tau using intracerebral injections and CSF sampling, and the modulation of AQP4 function, in a mouse model that develops tau NFT pathology (Ramsden et al., 2005) similar to that seen in neurodegenerative diseases such as Alzheimer’s disease (Braak and Braak, 1995). Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.