The plasma contact system is activated at early disease stages in AD mice and temporally correlated with astrocyte and microglia/macrophage activation in the brain. (A) Representative western blots probed with an antibody against mouse HK (mHK) light chain showing plasma HK levels in AD mice and their WT littermates at 2, 3, and 6 months of age. (B) The levels of HKi (sum of mHK and mHK-∆D5 bands) normalized to transferrin were similar in AD mice compared with WT littermates at 2 months of age, but levels of HKi were significantly lower in AD mice compared with WT littermates at 3 and 6 months of age. (C) Representative western blots probed with antibodies against GFAP and Iba-1 show astrocyte and microglia/macrophage activation in AD and WT mice at 2, 3, and 6 months of age. (D) GFAP expression was similar between AD mice and their WT littermates at 2 months of age, but was significantly increased in AD mouse brain compared with that of WT littermates at 3 and 6 months of age, indicating the onset and prolonged activation of astrocytes in the AD mouse brain. (E) At 2 and 3 months of age, expression levels of Iba-1 were similar between AD mice and their WT littermates. However, microglia/macrophage activation was significantly higher in AD mouse brain compared with brains of WT mice at 6 months of age. Student t test; n = 12 mice per group per age. All values presented as mean ± standard error of the mean (SEM). Results are from 2 independent experiments. GAPDH, glyceraldehyde-3-phosphate dehydrogenase; n.s., not significant.