Table 1.

Currently proposed brain waste clearance systems

System	Components and clearance location
“Paravascular pathway” and “glymphatic” system	Subarachnoid space → periarterial, periarteriolar, and pericapillary spaces → interstitial space → perivenous spaces → venous blood/cervical lymph nodes (e.g. along the venous walls)
“Intramural periarterial drainage” (IPAD) pathway	Interstitial space → basement membranes of the capillaries in the pericapillary spaces, and basement membranes within the tunica media of the arterioles and arteries in the periarteriolar and periarterial spaces → cervical lymph nodes (along the arterial walls)
Blood–brain barrier	Direct vascular transport (e.g. transport of β-amyloid via the LRP1)
Scavenger cells	Intracellular and extracellular brain waste degradation
Cerebrospinal fluid	Arachnoid villi and granulations → venous blood; Blood-CSF barrier at the choroid plexuses; Lymphatic pathways
Perineural (cranial and spinal) lymphatic drainage	Subarachnoid space → perineural space (e.g. peri-olfactory lymphatic drainage → cribiform plate → nasal lymphatics) → cervical lymph nodes
Meningeal lymphatic vessels	Subarachnoid space → meningeal lymphatic vessels → cervical lymph nodes

CSF, cerebrospinal fluid; LRP1, low-density cholesterol receptor-related protein-1