TABLE 3.

Pathways mediating pathological tau uptake into neurons.

Pathways	Forms of tau	Recipient cells	Subsequent activities inside the recipient cell	References
Exosome	Monomeric or oligomeric tau from exosomes derived from AD patient CSF, pT181 tau	Neuron	Seeding and Propagation	Saman et al., 2011; Wang et al., 2017
Clathrin-independent endocytosis	Monomeric tau	Neuron	Seeding and inducing aggregates, rupture endosome to activate Galectin8-NDP52 mediated autophagic degradation of monomeric tau	Falcon et al., 2019
HSPG-mediated direct translocation	GFP-tagged tau repeat domain	Neuron	Seeding and Propagating	Katsinelos et al., 2018; Merezhko et al., 2018
Bulk endocytosis	LMW tau aggregates and short fibrils	Neuron	Clogging up UPS and AELN	Wu et al., 2013
Tunneling nanotube	Exogenous Tau monomers and fibrils	Neuron	Unknown	Tardivel et al., 2016
HSPG-dependent macropinocytosis	Full-length tau fibrils	Neuron	Seeding and Propagating	Holmes et al., 2013; Puangmalai et al., 2020
Clathrin-dependent endocytosis	Exogenous TauP301L-GFP aggregates	Neuron	Rupture endosome to propagate, which can be inhibited by neuronal BIN1 isoform	Calafate et al., 2016