LAUSR

Alzheimer's disease (AD) is a progressive neurodegenerative disease which is characterized by the accumulation of amyloid-β peptide (Aβ). Orexin-A is a neuropeptide which has been reported to participate in the pathogenesis of AD. Thus, we aimed to investigate the possible mechanism by which Orexin-A acts in AD. APP/PS1 transgenic mice, an animal model of AD, were intracerebroventricularly injected with Orexin-A. Aβ-treated SH-SY5Y cells were used as a cell model of AD and treated with Orexin-A. The Morris water maze test, fluorescence microscopy, enzyme-linked immunosorbent assay (ELISA), electron microscopy, real-time PCR, and other biochemical assays were conducted. The Morris water maze test showed that Orexin-A aggravated cognitive deficit in APP/PS1 mice. Using thioflavine-S staining and ELISA, we found that Orexin-A promoted Aβ accumulation in APP/PS1 mice. By evaluating mitochondrial morphology, cytochrome c oxidase activity, ATP level, mitochondrial DNA copy number, and reactive oxygen species, we found that Orexin-A aggravated mitochondrial impairment in APP/PS1 mice and Aβ-treated SH-SY5Y cells. Our results indicate that Orexin-A exacerbates AD by inducing mitochondrial impairment. This is a new mechanism that explains how Orexin-A participates in the pathogenesis of AD.