PSEN1 and hyperinsulinemic hypoglycemia, familial, 4: Similarly, double transgenic amyloid precursor protein/presenilin 1 (APP/PS1) mice, characterized by sleep disturbances, display significant upregulation of pre-pro-orexin mRNA and OXA in the brain compared to the age-matched wild type (Zhao et al. 2022), while orexin deficiency markedly decreased A-beta pathology in the same transgenic mice (Roh et al. 2014).