fig3

Figure 3. Mechanism of action of tau protein clearance. (1) Intracellular clearance: antibodies can cross the BBB and enter the neuron, and then enter the cell either mediated by FcR or through endocytosis. Intracellularly, antibodies can bind to tau aggregates within the endosomal-lysosomal system and promote their breakdown, thereby increasing the pathway for lysosomal enzymes to degrade the aggregates while isolating tau assemblies in the cytoplasm and preventing their release from neurons or promoting proteasomal degradation through the binding of the E3 ubiquitin-protein ligase TRIM21. (2) Extracellular clearance: extracellular antibodies act to block the spread of tau pathology between neurons by isolating tau aggregates, interfering with their assembly, and promoting phagocytosis by microglia.