Depletion of plasma FXII improves cognitive function in AD mice. Spatial learning and memory retention of WT and AD mice were assessed by using the Barnes maze after 4 months of treatment with FXII-ASO or CTL-ASO. (A) During training trials, latency to poke the target hole was measured. (B-D) During the probe trials, latency to reach the closed target hole (B) and number of visits to the target hole (C) were measured. (D) Locomotor function was measured by the total distance traveled during the probe trials (one-way ANOVA; n = 9-14 mice per group). Results are from 3 independent experiments. Cognitive function of WT and AD mice treated with FXII-ASO or CTL-ASO was measured by contextual fear conditioning. (E) Freezing behavior was measured before electric foot shock during the training day to assess the basal freezing tendency of each group of mice. (F) Contextual memory was assessed by measuring freezing behavior upon re-exposure to the training chamber 24 hours after fear conditioning training (two-way ANOVA; n = 9-14 mice per group). Results are from 3 independent experiments.