Obstructive sleep apnoea and Alzheimer's disease: In search of shared pathomechanisms

Abstract

Alzheimer's disease (AD) is a significant public health concern. The incidence continues to rise, and it is set to be over one million in the UK by 2025. The processes involved in the pathogenesis of AD have been shown to overlap with those found in cognitive decline in patients with Obstructive Sleep Apnoea (OSA). Currently, the standard treatment for OSA is Continuous Positive Airway Pressure. Adherence to treatment can, however, be an issue, especially in patients with dementia. Also, not all patients respond adequately, necessitating the use of additional treatments. Based on the body of data, we here suggest that excessive and prolonged neuronal activity might contribute to genesis and acceleration of both AD and OSA in the absence of appropriately structured sleep. Further, we argue that external factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain, and further promote disease progression. If this hypothesis is proven in future studies, it could have far-reaching clinical translational implications, as well as implications for future treatment strategies in OSA.

Keywords: Alzheimer’s disease; Astrocytes; Neuroinflammation; Obstructive sleep apnea.

Fig. 1

The schematic representation of proposed shared mechanisms between Alzheimer’s Disease (AD) and Obstructive Sleep Apnoea (OSA) (also refer to the text). Abbreviations: SWS: slow wave sleep; Aβ: amyloid-β peptide; APOE ε4: apolipoprotein E (APOE) ε4; TLR2: Toll-like receptor 2.

Fig. 2

Proposed effects of disturbed sleep and altered neuronal activity at the level of multipartite synapse (A) (adapted from(Fellin et al., 2006, Xanthos and Sandkuhler, 2014). Increased clearance of metabolites has been postulated to occur during sleep, due to a low noradrenergic tone and decrease in astrocyte volume, resulting in increased extracellular space and increased glymphatic flow(B). (for in depth explanation refer to the main text). Abbreviations: NA: noradrenaline; ECS: extracellular space; Aβ: amyloid-β peptide; CSF: cerebrospinal fluid; ISF; interstitial fluid.