Table 2.

Clearance of Aβ and tau from the brain

Clearance system	Aβ9,16,44,109,125	Tau135,210
Blood–brain barrier clearance	Majority of eAβ clearance LRP1 efflux ABCB1 efflux ApoE-mediated efflux α2M–mediated efflux LRP2-mediated efflux RAGE influx	Unknown
Degradation clearance
Intracellular	Ubiquitin–proteasome pathway Autophagy–lysosome pathway Endosome–lysosome pathway Proteases	Ubiquitin–proteasome pathway Autophagy–lysosome pathway Endosome–lysosome pathway Proteases
Extracellular	Proteases Glial phagocytosis	Unknown
ISF bulk flow clearance
CSF sink	Contributes to eAβ clearance	Unknown
Perivascular drainage	Contribution % to eAβ clearance unknown	Unknown
Perivascular glymphatic	Contributes to eAβ clearance (55–65%) Likely to facilitate blood–brain barrier clearance	Might contribute to clearance of non-endocytosed tau
CSF absorption clearance
Circulatory	Arachnoid villi Blood–CSF barrier transporters (e.g. LRP1 efflux)	Arachnoid villi
Lymphatic	CSF lymphatic absorption	Unknown

Abbreviations: α2M, α2-macroglobulin; Aβ, amyloid- β; ABCB1, multidrug resistance protein 1 (also known as P-glycoprotein 1); ApoE, apolipoprotein E; CSF, cerebrospinal fluid; e-tau, extracellular tau; eAβ, extracellular Aβ; ISF, interstitial fluid; LRP, LDL receptor-related protein; RAGE, advanced glycosylation end product-specific receptor.