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. 2020 Oct 16;13:586731. doi: 10.3389/fnmol.2020.586731

FIGURE 3.

FIGURE 3

Pathways Mediating Pathological Tau Release and Uptake in Neurons and Glial Cells. (A) Neurons release pathological tau through the following pathways: (1) Exosomes; (2) HSPG-mediated direct translocation; (3) Ectosome; (4) Autophagy-based unconventional secretion; (5) Tunneling nanotube. Neurons can internalize pathological tau through the following pathways: (1) HSPG-mediated macropinocytosis; (2) HSPG-mediated direct translocation; (3) Bulk endocytosis; (4) Clathrin-dependent endocytosis; (5) Clathrin-independent endocytosis; (6) Exosomes; (7) Tunneling Nanotube. (B) Microglial cells internalize tau through exosome and phagocytosis. Microglia can also take up antibody-bound tau fibrils. Internalized tau can be degraded or packaged into exosomes and propagate. The receptor on the microglial cell surface that recognizes pathological tau is yet to be defined. (C) Astrocytes take up tau fibrils through HSPG-mediated macropinocytosis and tau monomers through an HSPG-independent pathway that needs further investigation. (D) The molecular pathways responsible for tau uptake in oligodendrocytes remain elusive.