Sleep deprivation accelerates the progression of alzheimer's disease by influencing Aβ-related metabolism

Sleep disorders have previously been connected with the neurodegenerative pathology of Alzheimer's disease (AD) due to the aggregation of beta-amyloid(A beta)peptides and tau proteinsinduced by sleep deprivation (SD). However, the underlying mechanisms remain unclear. Therefore, this study was performed to clarify how A beta-related metabolism is regulated after SD. Three-month-old Sprague-Dawley rats (250-300 g) were randomly divided into 5 groups: two SD groups(i.e.,SD-2d and SD-4d), two platform control groups(i.e.,PC-2d and PC-4d) and a home cage control group (CC). For the two SD groups, the modified multiple platform method (MMPM) was used to induce SD.Our experiments confirmed that SD impaired cognitive function and increased the levels of A beta peptides, a hallmark of AD. Additionally, we found that SD significantly increasedthe levels of the beta-site amyloid precursor protein (APP)-cleaving enzyme I (BACE1, beta-secretase), but had little impacton the levels of AP-degradationenzymes.This result may be the main cause of the over-expression of A beta 1-42 and A beta 1-40. Our results suggested that SD accelerates the progression of AD bymodulating A beta-related metabolism. This findinghasimportant implications for the diagnosis and prevention of AD. (C) 2017 Elsevier B.V. All rights reserved.