Unlike amyloid, tau does not associate with blood vessels, and the neuroinflammation leading to the amyloid related imaging abnormalities (ARIA) seen with some monoclonal amyloid antibodies has not been seen with tau antibodies. However, overactivation of the immune system remains a theoretical concern, and RO 7,105,705 (RG 6100) is a monoclonal IgG4 antibody against the N-terminal that was developed with reduced effector function to limit microglia activation, under the rationale that sequestration of eTau may be sufficient to prevent further seeding. [109] Reportedly, high doses were tolerated in the Phase 1 study on 74 healthy controls and patients with mild AD (NCT02820896), and a follow-up study Phase 2 study TAURIEL (NCT03289143) has been started in 360 patients with prodromal or mild AD, with results expected in September 2022.
