Chronic Sleep Restriction Induces A Accumulation by Disrupting the Balance of A Production and Clearance in Rats

Amyloid- (A) plays an important role in Alzheimer's disease (AD) pathogenesis, and growing evidence has shown that poor sleep quality is one of the risk factors for AD, but the mechanisms of sleep deprivation leading to AD have still not been fully demonstrated. In the present study, we used wild-type (WT) rats to determine the effects of chronic sleep restriction (CSR) on A accumulation. We found that CSR-21d rats had learning and memory functional decline in the Morris water maze (MWM) test. Meanwhile, A(42) deposition in the hippocampus and the prefrontal cortex was high after a 21-day sleep restriction. Moreover, compared with the control rats, CSR rats had increased expression of -site APP-cleaving enzyme 1 (BACE1) and sAPP and decreased sAPP levels in both the hippocampus and the prefrontal cortex, and the BACE1 level was positively correlated with the A(42) level. Additionally, in CSR-21d rats, low-density lipoprotein receptor-related protein 1 (LRP-1) levels were low, while receptor of advanced glycation end products (RAGE) levels were high in the hippocampus and the prefrontal cortex, and these transporters were significantly correlated with A(42) levels. In addition, CSR-21d rats had decreased plasma A(42) levels and soluble LRP1 (sLRP1) levels compared with the control rats. Altogether, this study demonstrated that 21 days of CSR could lead to brain A accumulation in WT rats. The underlying mechanisms may be related to increased A production via upregulation of the BACE1 pathway and disrupted A clearance affecting brain and peripheral A transport.