Fig. 1
From: LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression
Chronic LRRK2 inhibition is well-tolerated in wild-type and LRRK2G2019S KI mice. a LRRK2G2019S KI mice and wild-type littermates at 3 months of age were injected with tau paired helical filaments (PHFs) derived from Alzheimer’s disease brains. At the same time, mice were given access to diet with 0, 75, or 450 mg/kg MLi-2 incorporated. At 3 or 6 months post-injection, mice were sacrificed, and the primary endpoint of brain pathology was assayed. Secondary studies of PK/PD as well as lung and kidney histology were also assayed. b Average mouse weights over 3 months of 0 or 450 mg/kg MLi-2 treatment. c Average mouse weights over 6 months of 0, 75, or 450 mg/kg MLi-2 treatment. d Estimated exposure of mice in the 3-month cohorts to MLi-2 based on diet consumption. e Estimated exposure of mice in the 6-month cohorts to MLi-2 based on diet consumption. Mice on the 450 mg/kg diet averaged 48 mg/kg/day exposure to MLi-2, while mice on the 75 mg/kg diet averaged 8 mg/kg/day exposure. Plots display the mean and standard error of each cohort at each time point