Complement Proteins in Serum Astrocyte-Derived Exosomes Are Associated with Poststroke Cognitive Impairment in Type 2 Diabetes Mellitus Patients

Article type: Research Article

Authors: Wu, Yaxuan^{a; b; 1} | Tan, Ming^{b; 1} | Gao, Yanling^b | Geng, Na^b | Zhong, Weibin^b | Sun, Hairong^b | Li, Zhenguang^b | Wu, Chenxi^d | Li, Xuemei^{c; *} | Zhang, Jinbiao^{b; *}

Affiliations: [a] Weifang Medical University, Weifang, Shandong, China | [b] Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China | [c] Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China | [d] Department of Central Sterile Supply Department, Xichang People’s Hospital, Xichang, Liangshan Yi Autonomous Prefecture, Sichuan, China

Correspondence: [*] Correspondence to: Xuemei Li, Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, China. Email: [email protected] and Jinbiao Zhang, Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, 264200, China. Email: [email protected].

Abstract: Background:The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer’s disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods:This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results:Mediation analyses showed that C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions:Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients.REGISTRATION: URL: http://www.chictr.org.cn/,ChiCTR1900021544

Keywords: Keywords: Alzheimer’s disease, astrocyte-derived exosomes, complement proteins, post stroke cognitive impairment, type 2 diabetes mellitus

DOI: 10.3233/JAD-231235

Journal: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 291-305, 2024