MAPT and Alzheimer disease: While tau is an intracellular protein, secreted abnormal forms may propagate through synaptic networks in AD in a prion-like process, and via secreted extracellular vesicles, hence rendering extracellular tau clearance pathophysiologically important.7,25-28 Our data could be compatible with a model including constitutive drainage of phosphorylated tau species into the CLNs via glymphatic and lymphatic mechanisms that reduces with age, leading to greater tau accumulation in the extracellular compartment.