Obstructive sleep apnea may induce orexinergic system and cerebral β-amyloid metabolism dysregulation: is it a further proof for Alzheimer's disease risk?

Abstract

BackgroundObstructive Sleep Apnea (OSA) is associated with pathological changes of cerebral β-amyloid dynamics. Orexin has been demonstrated interfering with β-amyloid metabolism in Alzheimer's Disease (AD) pathology. The present study investigated cerebrospinal-fluid (CSF) β-amyloid40 (Aβ40), β-amyloid42 (Aβ42) and orexin levels in OSA patients compared to AD patients and controls. MethodsOSA and AD patients were included in this study and compared to a group of controls. Patients and controls underwent lumbar puncture for the assessment of CSF Aβ40, Aβ42, tau proteins, orexin levels, and polysomnography to measure nocturnal sleep architecture. Results20 OSA patients, 20 AD patients, and 15 controls were included in our study. OSA patients showed higher CSF orexin levels than AD patients and controls, and AD patients showed higher CSF orexin levels than controls. Moreover, CSF Aβ40 and Aβ42 were lower in OSA patients than controls, but higher in OSA patients compared to AD patients. However, AD patients showed lower CSF Aβ42 levels but comparable CSF Aβ40 levels than controls. Sleep macrostructure was similarly altered in OSA and AD patients compared to controls. Finally, the apnea-hypopnea index (AHI) was related to the ratio Aβ42/Aβ40 and CSF orexin levels in OSA patients. ConclusionThis study proved the alteration of CSF orexin levels and β-amyloid isoforms 40 and 42 in OSA patients. We suppose that sleep disruption and intermittent hypoxia, the two core features of OSA, may induce orexinergic system and cerebral β-amyloid metabolism dysregulation. This evidence further supports the current hypothesis that OSA may possibly start AD neuropathological processes.