| First Author | Bajracharya R | Year | 2021 |
| Journal | Acta Neuropathol Commun | Volume | 9 |
| Issue | 1 | Pages | 42 |
| PubMed ID | 33712083 | Mgi Jnum | J:311555 |
| Mgi Id | MGI:6771454 | Doi | 10.1186/s40478-021-01147-0 |
| Citation | Bajracharya R, et al. (2021) Tau antibody isotype induces differential effects following passive immunisation of tau transgenic mice. Acta Neuropathol Commun 9(1):42 |
| abstractText | One of the main pathological hallmarks of Alzheimer's disease (AD) is the intraneuronal accumulation of hyperphosphorylated tau. Passive immunotherapy is a promising strategy for the treatment of AD and there are currently a number of tau-specific monoclonal antibodies in clinical trials. A proposed mechanism of action is to engage and clear extracellular, pathogenic forms of tau. This process has been shown in vitro to be facilitated by microglial phagocytosis through interactions between the antibody-tau complex and microglial Fc-receptors. As this interaction is mediated by the conformation of the antibody's Fc domain, this suggests that the antibody isotype may affect the microglial phagocytosis and clearance of tau, and hence, the overall efficacy of tau antibodies. We therefore aimed to directly compare the efficacy of the tau-specific antibody, RN2N, cloned into a murine IgG1/kappa framework, which has low affinity Fc-receptor binding, to that cloned into a murine IgG2a/kappa framework, which has high affinity Fc-receptor binding. Our results demonstrate, for RN2N, that although enhanced microglial activation via the IgG2a/kappa isotype increased extracellular tau phagocytosis in vitro, the IgG1/kappa isoform demonstrated enhanced ability to reduce tau pathology and microgliosis following passive immunisation of the P301L tau transgenic pR5 mouse model. |
