The kavalactone Methysticin (6 mg/kg) is administered once a week for a period of 6 months to 6 month old transgenic APP/Psen1 mice by oral gavage. Methysticin treatment activates the Nrf2 pathway in the hippocampus and cortex of mice. The Aβ deposition in brains of Methysticin-treated APP/Psen1 mice is not altered compared to untreated mice. However, Methysticin treatment significantly reduces microgliosis, astrogliosis and secretion of the pro-inflammatory cytokines TNF-α and IL-17A. Methysticin treatment results in a significant activation of the Nrf2/ARE pathway in hippocampus and the cortex but not in the midbrain and cerebellum of ARE-luciferase reporter gene mice. Methysticin treatment significantly increases the expression of both genes compared to untreated animals^[2].