(A) Schematic of sAPP icv infusion by 7-d osmotic mini-pump in adult wild type mice. (B, C) Analysis of cell proliferation in SVZ (B) and dentate gyrus (DG) (C) by quantification of Ki67 positive cells after icv infusion of sAPPα or Veh (n = 9 mice per group). (D, E) Analysis of cell proliferation in SVZ (D) and DG (E) by quantification of Ki67 positive cells after icv infusion of sAPPβ or Veh (n = 5 mice per group). (F) Schematic of App ChPl gain-of-function model involving a single icv injection of AAV5 expressing mouse App or eGFP (control) in wild type mice. (G) Quantitative PCR analysis of App expression in ChPl after AAV5 icv injection (AAV5-mAPP n = 4 mice, AAV5-eGFP n = 3 mice). (H, I) Analysis of cell proliferation in SVZ (H) and DG (I) by quantification of Ki67 positive cells after icv injection (AAV5-mAPP n = 6 mice, AAV5-eGFP n = 5 mice). *P < 0.05; **P < 0.01; ***P < 0.001; t test; all values, mean ± SD. ChPl, choroid plexus; Hc, hippocampus; SVZ, ventricular-subventricular zone; DG, dentate gyrus; icv, intracerebroventricular; Veh, vehicle.