Regulation of Sleep Behavior by Overexpression of Amyloid Precursor Protein in Drosophila Neurons

Abstract

Amyloid precursor protein (APP) can generate neurotoxic β-amyloid 42 (Aβ42) by proteolytic process, which plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Individuals with mild to moderate AD exhibit sleep disturbance, even before the onset of AD. The purpose of this study is to verify the effect of APP on sleep behavior by using an APP overexpressing Drosophila AD model. APP-overexpressed flies were grouped by age, and their sleep amounts were monitored. Our results demonstrated that APP overexpression had no impacts on sleep amounts in young (4–7 days after eclosion, 4–7AE) flies. However, APP overexpression contributed to lower day and total sleep amounts in the middle-aged (11–14AE) flies. Moreover, old-aged (40AE) flies with overexpressing APP exhibited increased number of sleep bouts and decreased sleep time, indicating sleep fragmentation in these flies. Our results indicated that overexpression of APP in neurons has distinct effects on sleep behavior at different ages, but the specific mechanisms underlying the sleep regulation by APP are needed for further study. In addition, our data also suggest that sleep disturbance in AD animals can be caused by APP expression alterations, which provide a potential treating target for sleep intervention and therapy for AD patients.