17-LB: Disruption of Circadian Clocks Promote Progression of Alzheimer’s Disease in Diabetic Mice

Abstract

Almost all plants and animals exhibit inherent 24-hour oscillations to adapt the Earth’s rotation. The main function of circadian rhythm was to prepare an organism for the potential outer opportunities and challenges. Alzheimer’s disease (AD) is a progressive neurodegenerative disease, which is more popular in patients with type 2 diabetes mellitus (T2DM). However, the effects of circadian disorder on mental and physical health for T2DM patients are not yet fully understood, even though circadian disruption has been confirmed to promote the progression of AD in population. By housing db/db mice on a disrupted (6:18 light/dark cycle) circadian rhythm, we assessed the circadian gene expression, body weight, cognitive ability and AD-related pathophysiology. Our results indicated housing in these conditions had disrupted diurnal circadian rhythms in hippocampus and contributed to weight gain. In the brain, circadian-disrupted db/db mice showed a decreased cognitive ability and an increased hyperphosphorylation of tau protein, even though no difference was found in Aβ deposition. We also found that the hyperphosphorylated tau protein exhibited more disruptive daily oscillations in db/db mice hippocampus under 6:18 light/dark cycle. In conclusion, circadian alterations could promote the development of AD in the patients of T2DM. Disclosure J. Huang: None. Funding National Natural Science Foundation of China (81670754, 81800686, 81974114)