Complement proteins in serum astrocyte-derived exosomes are associated with mild cognitive impairment in type 1 diabetes mellitus patients

Xiaoxiao Qi; Yingxiao Liu; Haiyan Chi; Yachao Yang; Qiao Xiong; Mengfan Li; Ran Yao; Hairong Sun; Zhenguang Li; Jinbiao Zhang

doi:10.1016/j.neulet.2023.137318

Complement proteins in serum astrocyte-derived exosomes are associated with mild cognitive impairment in type 1 diabetes mellitus patients

Neurosci Lett. 2023 Jul 27:810:137318. doi: 10.1016/j.neulet.2023.137318. Epub 2023 Jun 2.

Authors

Xiaoxiao Qi¹, Yingxiao Liu², Haiyan Chi², Yachao Yang², Qiao Xiong¹, Mengfan Li³, Ran Yao³, Hairong Sun³, Zhenguang Li⁴, Jinbiao Zhang⁵

Affiliations

¹ Department of Clinical Medicine, Weifang Medical University, Weifang, Shandong 261053, China; Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China.
² Department of Endocrinology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China.
³ Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China.
⁴ Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China. Electronic address: lzg6598@126.com.
⁵ Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China. Electronic address: drzhangjinbiao@163.com.

PMID: 37271220
DOI: 10.1016/j.neulet.2023.137318

Abstract

Background: The complement system plays a crucial role in cognitive impairment. The aim of this study is to investigate the correlation between the complement proteins levels in serum astrocyte-derived exosomes (ADEs) and mild cognitive impairment (MCI) in type 1 diabetes mellitus (T1DM) patients.

Methods: In this cross-sectional study, the patients with immune-mediated T1DM were enrolled. Healthy subjects matched for age and sex with T1DM patients were selected as controls. The cognitive function was evaluated by a Beijing version of the Montreal Cognitive Assessment (MoCA) questionnaire. The complement proteins including C5b-9, C3b and Factor B in serum ADEs were measured by ELISA kits.

Results: This study recruited 55 subjects immune-mediated T1DM patients without dementia, including 31 T1DM patients with MCI, 24 T1DM patients without MCI. 33 healthy subjects were enrolled as controls. The results showed higher complement proteins including C5b-9, C3b and Factor B levels in ADEs from T1DM patients with MCI than those in the controls (P < 0.001, P < 0.001, P = 0.006) and T1DM patients without MCI (P = 0.02, P = 0.02, P = 0.03). The C5b-9 levels in ADEs were independently associated with MCI in T1DM patients(OR: 1.20, 95% CI: 1.00-1.44, P = 0.04). The C5b-9 levels in ADEs were significantly correlated with global cognitive scores (β = -0.360, P＜0.001) and visuo-executive (β = -0.132, P＜0.001), language(β = -0.036, P = 0.026) and delayed recall score (β = -0.090,P = 0.007). There was no correlation between the C5b-9 levels in ADEs and the fasting glucose, HbA1c, fasting c-peptide and GAD65 antibody in T1DM patients. Furthermore, the C5b-9, C3b and Factor B levels in ADEs exhibited a fair combined diagnostic value for MCI, with an area under the curve of 0.76 (95% CI: 0.63-0.88, P = 0.001).

Conclusion: The elevated C5b-9 levels in ADEswere significantly associated with theMCI in T1DM patients. The C5b-9 in ADEs may be used as a marker of MCI in T1DM patients.

Keywords: Astrocyte-derived exosomes; Complement proteins; Mild cognitive impairment; Type 1 diabetes mellitus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Astrocytes / metabolism
Cognitive Dysfunction* / diagnosis
Complement Factor B / metabolism
Complement Membrane Attack Complex / metabolism
Cross-Sectional Studies
Diabetes Mellitus, Type 1* / complications
Exosomes* / metabolism
Humans

Substances

Complement Membrane Attack Complex
Complement Factor B