Intracellular Tau Clearance by Immunotherapy Mediated by TREM21

Our findings suggest that intranasally administered TTCM2-ms rapidly distributes across the brains of tauopathy mice. Further, TTCM2-ms recognized and cleared pathological tau from the intracellular and synaptic compartments of neuronal cells via TRIM21, thus improving cognitive functions. This study provides insights into the mechanisms of an effective tau immunotherapy strategy against intracellular tau pathology in neurodegenerative tauopathies, including AD.