Recent research suggests that disruptions in circadian rhythms, including sleep-wake cycles, are early signs of Alzheimer's disease (AD) and may contribute to the pathological processes. The Amyloid Precursor Protein (APP) plays a key role in AD because when cleaved by β- and γ-secretase, it generates the toxic β-amyloid fragments. However, when α-secretase activity is followed by γ-secretase cleavage of APP, no β-amyloid is produced. Interestingly both APP processing pathways produce the same C-terminal APP intracellular domain (AICD), which has been linked to transcription regulation. Previous studies in Drosophila have shown that overexpression of α-secretase, β-secretase, or AICD in circadian pacemaker neurons disrupted locomotor activity rhythms. These studies suggest that the misregulation of APP processing and the consequent changes in AICD localization may contribute to the pathological processes in AD. To investigate how changes in the AICD function may contribute to AD, we used transgenic flies with induced AICD expression in circadian pacemaker neurons or mushroom body neurons.