Amyloid β and tau are involved in sleep disorder in Alzheimer's disease by orexin A and adenosine A(1) receptor

Zhenhua Liu, Fumin Wang, Minglu Tang, Yongjun Zhao, Xiaoting Wang
International Journal of Molecular Medicine 2019, 43 (1): 435-442
Sleep disorder is confirmed as a core component of Alzheimer's disease (AD), while the accumulation of amyloid β (Aβ) in brain tissue is an important pathological feature of AD. However, how Aβ affects AD‑associated sleep disorder is not yet well understood. In the present study, experiments on animal and cell models were performed to detect the association between sleep disorder and Aβ. It was observed that Aβ25‑35 administration significantly decreased non‑rapid eye movement sleep, while it increased wakefulness in mice. In addition, reverse transcription‑quantitative polymerase chain reaction and western blot analysis revealed that the expression levels of tau, p‑tau, orexin A and orexin neurons express adenosine A1 receptor (A1R) were markedly upregulated in the brain tissue of AD mice compared with that in samples obtained from control mice. Furthermore, the in vitro study revealed that the expression levels of tau, p‑tau, orexin A and adenosine A1R were also significantly increased in human neuroblastoma SH‑SY5Y cells treated with Aβ25‑35 as compared with the control cells. In addition, the tau inhibitor TRx 0237 significantly reversed the promoting effects of Aβ25‑35 on tau, p‑tau, orexin A and adenosine A1R expression levels, and adenosine A1R or orexin A knockdown also inhibited tau and p‑tau expression levels mediated by Aβ25‑35 in AD. These results indicate that Aβ and tau may be considered as novel biomarkers of sleep disorder in AD pathology, and that they function by regulating the expression levels of orexin A and adenosine A1R.

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