Increase in Aβ deposition and wakefulness by rescue of orexin expression in APP/PS1/OR^−/− mice via expression of orexin with lentiviral vector driven by hypocretin/orexin promoter in the bilateral hypothalamus. (A–C) Amount of Aβ pathology in the hippocampus and cortex of the APP/PS1-21/OR^−/− mice after bilateral injection of hypocretin promoter–driven orexin lentiviral vector in the hypothalamus of the APP/PS1/OR^−/− mice was compared with results from injection of the same lentiviral vector overexpressing GFP. (D) The amount of wakefulness as measured by polysomnography was compared between the same groups of mice. Each mouse was investigated independently one time. Data are presented as mean ± SEM (n = 6–7 in each group, two-tailed Student’s t test in C; n = 3 in each group, Mann–Whitney test in D). *, P < 0.05. Bar, 500 µm.