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

Background: Obstructive 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-amyloid (Aβ), β-amyloid (Aβ) and orexin levels in OSA patients compared to AD patients and controls.

Methods: OSA 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 Aβ, Aβ, tau proteins, orexin levels, and polysomnography to measure nocturnal sleep architecture.

Results: 20 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 Aβ and Aβ were lower in OSA patients than controls, but higher in OSA patients compared to AD patients. However, AD patients showed lower CSF Aβ levels but comparable CSF Aβ 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 Aβ/Aβ and CSF orexin levels in OSA patients.

Conclusion: This 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.