Obstructive sleep apnea and Alzheimer’s disease-related cerebrospinal fluid biomarkers in mild cognitive impairment

Abstract

<jats:title>Abstract</jats:title> <jats:p>Previous studies have demonstrated that sleep-breathing disorders, and especially obstructive sleep apnea (OSA), can be observed in patients with higher risk of progression to Alzheimer’s disease (AD). Recent evidence indicates that cerebrospinal fluid (CSF) AD-biomarkers are associated with OSA. In this study, we investigated these associations in a sample of patients with Mild Cognitive Impairment (MCI), a condition that is considered the first clinical phase of AD, when patients showed biomarkers consistent with AD pathology. Fifty-seven patients (mean age=66.19; SD=7.13) with MCI were included in the study. An overnight polysomnography recording was used to assess objective sleep parameters (i.e., Apnea/hypopnea index, total sleep time, sleep efficiency, sleep latency, arousal index, awakening, stage 1, 2, and slow wave sleep and REM sleep, periodic limb movement index, O2 saturation during sleep, and percentage of time O2 saturation &amp;lt;90%). Phosphorylated-tau (P-tau), total-tau (T-tau) and amyloid beta 42 (Aβ42) were measured in CSF. Unadjusted correlation analyses showed that a higher apnea/hypopnea index (reflecting higher OSA severity) was related to higher P-tau and T-tau (both results remained significant after Bonferroni correction, p=0.001). Importantly, these associations were observed even after adjusting for potential confounders (i.e., age, sex, Body Mass Index, sleep medication, smoking, hypertension, and heart disease). Although more research is needed to establish a causal link, our findings provide evidence that OSA could be related to the pathophysiological mechanisms involved in neurodegeneration in MCI patients.</jats:p>

WITHDRAWN: Sleep Treatment Improves Neuropsychological Symptoms and Reduces Blood Aβ42/pTau Protein in Alzheimer's Disease Patients: a Longitudinal Study

“…Studies in mouse models of Alzheimer's disease and in humans have convincingly demonstrated a tight association between sleep disorder and Alzheimer's disease in terms of amyloid peptides and Tau proteins 14,15,[43][44][45][46] . Increased cerebrospinal fluid and blood levels of amyloid peptides and phosphorylated Tau protein were reported in patients with sleep disturbances 9,16,17,[47][48][49] and have been considered as biomarkers for disease progression 11 . In this study, our data also showed a strong correlation between PSQI scores and blood levels of A42 and Tau-pT181, either before or after sleep intervention.…”

“…These sleep behavior changes began in the prodromal phase of Alzheimer's disease while patients only suffered from mild cognitive impairment, possibly due to amyloid/Tau pathology before cognition decline 14 . Recent studies showed that sleep deprivation or disturbances increased A peptides and Tau proteins in CSF solution compared to normal sleep controls 9,[15][16][17] due to elevated production of A peptides 18 , which was supported by studies from transgenic mouse models of Alzheimer's disease 19 . On the other hand, a healthy sleep cycle was shown to facilitate A clearance from the brain tissue 20 .…”

“…The A42 peptide is less soluble due to two extra hydrophobic amino acid residues at the C-terminus, rendering it more prone to aggregation than A40 8 . Currently, the levels of A40/A42 peptides in patient CSF and blood are implicated as disease biomarkers in the clinic 7,9 . Tau protein is a key component of microtubule assembly in axons and its function is regulated by phosphorylation on multiple residues including threonine 181 (Tau-pT181) 10 .…”

The Link Between Obstructive Sleep Apnoea and Neurodegeneration and Cognition

“…Concerning tau, the relationship between the protein and sleep apnoea is even less understood. While some studies found no association between OSA and CSF total, phosphorylated tau, or neurofibrillary tangles [14,15,43], others did, although it remains to be seen if these are caused by OSA itself or if they are age-related early manifestations of AD-related pathological processes [18,44,45]. With no AD treatment being available, prevention through treatment of risk factors is currently the only way to delay the onset of AD, with OSA being a viable target.…”

Assessment of Alzheimer’s disease-related biomarkers in patients with obstructive sleep apnea: A systematic review and meta-analysis

“…Currently, several efforts have been made to better understand the risk of sleep-disordered breathing (SDB), especially OSA, as a potential contributor to AD ( Liguori et al, 2017 ; Sharma et al, 2018 ; Jorge et al, 2020 ; Diáz-Román et al, 2021 ), while some studies questioned the link between OSA and AD ( Blackwell et al, 2015 ; Mohajer et al, 2020 ). Evidence indicated that no associations were observed between the SDB parameters and clinically significant cognitive decline ( Blackwell et al, 2015 ; Jorge et al, 2020 ).…”