Alzheimer’s Disease Biomarkers and Complement Proteins Mediate the Impact of Sleep Fragmentation on Cognitive Impairment in Obstructive Sleep Apnea Patients Without Dementia

Article type: Research Article

Authors: Yang, Yanyan^{a; b; 1} | Li, Mengfan^{a; 1} | Leng, Bing^a | Yao, Ran^a | Xue, Song^a | Tan, Ming^a | Sun, Hairong^a | Zhang, Jinbiao^{a; *}

Affiliations: [a] Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China | [b] Department of Neurology, The 88th Hospital of People’s Liberation Army, Tai’an, Shandong, China

Correspondence: [*] Correspondence to: Jinbiao Zhang, Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, 264200, China. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Cognitive impairment is common in patients with obstructive sleep apnea (OSA). Previous studies indicated that intermittent hypoxia, sleep fragmentation, and depressive symptoms were associated with cognitive impairment in OSA patients. Objective:The study aimed to investigate whether sleep characteristics and depressive symptoms affected cognitive abilities mediated by Alzheimer’s disease (AD) biomarkers and complement proteins in OSA patients without dementia. Methods:A total of 317 subjects without dementia who had undergone polysomnography, cognitive and neuropsychological evaluations, were recruited. Neuronal-derived exosomes (NDEs) levels for amyloid-β (Aβ), total tau (T-tau), and tau phosphorylated 62 at threonine 181 (P-T181-tau) and astrocyte-derived exosomes (ADEs) levels for complement proteins were measured. Mediation analysis were performed to explore the mediation effects of AD biomarkers (Aβ42, T-tau, P-T181-tau) and complement proteins (C3b and C5b-9) on cognition. Results:The findings revealed that the association between sleep fragmentation and cognition was mediated by Aβ42 (the percentage varied from 18.25% to 30.6%), P-T181-tau (the percentage varied from 24.36% to 32.3%), and C5b-9 (the percentage varied from 30.88% to 60.7%). The influence of depressive symptoms on cognition was only mediated via C3b (the percentage varied from 24.1% to 36.6%). Conclusions:In OSA patients without dementia, Aβ42 and P-T181-tau levels in NDEs, and C5b-9 levels in ADEs mediated the impact of sleep fragmentation on cognitive impairment, and C3b levels in ADEs mediated the impact of depressive symptoms on cognitive impairment.

Keywords: Alzheimer’s disease biomarkers, cognition function, complement proteins, depressive symptoms, obstructive sleep apnea, sleep characteristics

DOI: 10.3233/JAD-221288

Journal: Journal of Alzheimer's Disease, vol. 95, no. 4, pp. 1685-1696, 2023