Figure 2.

Receptor-mediated endocytosis of tau species is facilitated by several receptors. Central nervous system cells actively internalize monomeric tau via receptor-mediated endocytosis in addition to the HSPG-dependent pathway. Monomeric tau is internalized by muscarinic receptors M1 and M3 in neurons [43]. CX3CR1 mediates monomeric tau uptake in microglia [45]. For astrocytes, monomeric tau can be internalized in a non-HSPG dependent pathway [46]. Further work should be focused on identifying specific receptors of tau endocytosis. Additionally, LRP1 has recently been identified as a major regulator of tau spread in the brain [44]; LRP1 is abundantly expressed by microglia, astrocytes, and neuronal cells [47,48].