Figure 1.

Single mild closed head injury accelerates developing Alzheimer’s disease. a, Schematic illustration of the experimental protocol. WT and APP TG mice at two months of age received a single mild CHI, and all the assessments were made 30 days after TBI except for qPCR analysis. b, Expression of proinflammatory markers, vimentin (Vim) and cytokines (IL-1β, IL-6, TNFα), in the ipsilateral hippocampus is elevated by a single mild CHI in APP TG mice, but not in WT mice. The data are means ±SEM (ANOVA with Fisher's PLSD post-hoc test, n=3~5 animals/group). c, Single mild CHI facilitates formation of Aβ plaques in the brain of APP TG mice. Immunostaining analysis of 4G8 immunoreactivity. The data are means ±SEM (ANOVA with Bonferroni post-hoc test, n=5 animals/group). Scale bars: 400 μm. d, Single mild CHI accelerates neuropathological changes in TG mice. Immunoblot analysis of BACE1, TDP-43, AC-tau, and p-tau181 in the hippocampus of WT and TG mice that received a single mild CHI. The data are means ±SEM (ANOVA with Fisher's PLSD post-hoc test, n=3~4 animals/group). e, Single mild CHI expedites memory impairment in APP TG mice. The novel object recognition test was conducted in WT and TG mice 30 days after single mild CHI. The data are means ±SEM (ANOVA with Bonferroni post-hoc test, n=9~12 animals/group). f, Single mild CHI accelerates impairments in spatial learning and memory in APP TG mice. The Morris water maze test was conducted in WT and TG mice 30 days after single mild CHI. The data are means ±SEM. ***P<0.001 (ANOVA with repeated measures). The probe test was conducted 24 hours following 7-day learning acquisition training. The data are means ±SEM (ANOVA with Bonferroni post-hoc test, n=9~12 animals/group).