Significant increase of pro-apoptotic factors, CHOP and cleaved caspase-12 in 5×FAD mice. (a) Western blots analyses revealed that CHOP protein increased with age in 5×FAD mice (n = 7, *P < 0.05 vs. 2-month WT mice). (b) Western blots analysis showed that caspase-12 activation increased with age in 5×FAD mice (n = 6, *P < 0.05, †P < 0.01 vs. age-matched WT mice; ‡P < 0.05,§P < 0.01 vs. 2-month WT mice; ||P < 0.05 vs. 2-month 5×FAD mice). (c) Western blots analysis showed the expression of p-JNK/JNK. (d) Confocal images of CHOP (red), 6E10 (Aβ, green) and nuclei (DAPI, blue) in the cortical slices of 2-, 7-, and 12-month-old mice by immunofluorescence staining. Scale bars = 100 μm. (e) Confocal images of CHOP (green), GFAP (red) or β-III-tubulin (red) in the frontal cortical slices of 7-month-old 5×FAD mice by immunofluorescent staining. The bottom row of (e) indicates immunofluorescent staining of CHOP (red) and 6E10 (green, targeting Aβ). Scale bars = 10 μm. 5×FAD: Transgenic mice with five familiar Alzheimer's disease; WT: Wild-type mice; CHOP: CCAAT/enhancer-binding protein homologous protein; JNK: c-Jun amino-terminal kinase; Aβ: Amyloid β; 6E10: The antibody targeting Aβ; GFAP: Glial fibrillary acidic protein; DAPI: 6-diamidino-2-phenylindole.