Sleep Deprivation Induced Plasma Amyloid-β Transport Disturbance in Healthy Young Adults

Background: Sleep is an important physiological process and beneficial in the removal of brain metabolites and functional recovery. Prior studies have shown that sleep disorders are significant risk factors for Alzheimer's disease (AD). Objective: The present study was designed to characterize the effect of short-term total sleep deprivation (TSD) on plasma amyloid-β (Aβ) concentrations. Methods: A clinical trial was conducted between March 1, 2016, and April 1, 2016. Twenty volunteers (age 27.3±3.4 years) with normal cognitive function and sleeping habits were recruited from the local population. Participants underwent 24h of TSD. Periprocedural blood samples were collected to compare the changes of plasma Aβ₄₂, Aβ₄₀, low-density lipoprotein receptor-related protein (sLRP-1), soluble receptors for advanced glycation end products (sRAGE), and serum superoxide dismutase (SOD) and malonaldehyde (MDA). Results: TSD increased morning plasma Aβ₄₀ levels by 32.6% (p <0.001) and decreased the Aβ₄₂/Aβ₄₀ ratio by 19.3% (p <0.001). A positive relationship was found between TSD duration and plasma Aβ₄₀ level (r = 0.51, p <0.001) and Aβ₄₀/Aβ₄₂ ratio (r = 0.25, p = 0.003). Plasma concentrations of sLRP1 (p=0.018) and sRAGE (p=0.001) decreased significantly after TSD. Aβ₄₀ and Aβ₄₂ plasma concentrations correlated with plasma levels of sLRP1 and sRAGE. Serum SOD decreased after TSD (p=0.005), whereas serum MDA was increased (p=0.001). Conclusion: Sleep deprivation can lead to an elevation of plasma Aβ₄₀ and decrease of the Aβ₄₂/Aβ₄₀ ratio. The underlying mechanisms may be related to increased oxidative stress and impaired peripheral Aβ clearance as pathomechanisms of AD.