タウ免疫療法

抄録

Active and passive tau immunization has been shown to attenuate phenotypes in tauopathy model mice. So far, two tau vaccines and three anti–tau monoclonal antibodies have been subjected to clinical trials for patients with Alzheimer's disease or progressive supranuclear palsy. In the present study, we developed new monoclonal antibodies to hyperphosphorylated tau for future clinical use. Selected antibodies to pSer413–tau (Ta1505) and to pSer396–tau (Ta4 and Ta9) were injected intraperitoneally into aged mouse models of tauopathy once a week at 0.1 or 1mg/shot 5 times. Ta1505 antibody significantly improved memory in a dose–dependent manner, while Ta4 and Ta9 antibodies showed less effect. The cognitive improvement paralleled a reduction in the levels of tau hyperphosphorylation, tau oligomer accumulation, synapse loss, neurofibrillary tangle formation, and neuronal loss. Furthermore, Ta1505 antibody displayed suppressive effects against not only tau hyperphosphorylation but also Aβ oligomer accumulation in a different, aged mouse model of Alzheimer's disease. These results indicate that pSer413 is a promising target in the treatment of Alzheimer's disease and other tauopathies.