Effective immunotherapy occurs in neurons

 REBECCA M. NISBET Authors Info & Affiliations

Abstract

The main pathological hallmark of a group of neurodegenerative diseases called tauopathies is the formation of intracellular aggregates composed of the tau protein in the brain. Despite promising results in preclinical studies, tau immunotherapies in clinical development for the treatment of tauopathies, including Alzheimer’s disease, have thus far failed to improve patient cognition. Owing to its critical pathological role, most still argue that tau is an excellent therapeutic target. Therefore, better understanding of the mechanisms by which tau antibodies can remove pathogenic tau from the brain and how these processes can be exploited is paramount for the design of second-generation immunotherapies. On page 1336 of this issue, Mukadam et al. (1) show that the cytoplasmic antibody receptor and E3 ubiquitin ligase tripartite motif-containing 21 (TRIM21) is required for effective tau immunotherapy in a tauopathy mouse model, providing an area of focus for the development of future tau antibodies.

https://www.science.org/doi/10.1126/science.adg9800