Affiliations: [a]
School of Basic Medicine, Key Laboratory for Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China
| [b]
Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China
| [c]
Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, China
| [d] Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical, Ningxia Medical University, Yinchuan, China
Correspondence:
[*]
Correspondence to: Changchun Hei, School of Basic Medicine, Key Laboratory for Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China. E-mail: [email protected] and Qing Chang, Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical, Ningxia Medical University, Yinchuan, China. E-mail: [email protected].
Abstract: Background:Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is clinically characterized by progressive cognitive decline. Glucagon-like peptide-1 (GLP-1) is a hormone that belongs to the incretin family and is released in response to nutrient intake. It plays a role in maintaining metabolic homeostasis and has been suggested to be involved in maintaining the brain microenvironment. However, the role of GLP-1 in AD pathogenesis has not been fully illustrated. Objective:This study aims to investigate the clinical relevance of GLP-1 in AD and the effects of GLP-1 in amyloid-β (Aβ) metabolism in vitro. Methods:In this study, 39 AD patients and 120 cognitively intact controls were included. Plasma levels of GLP-1 were measured using ELISA. SH-SY5Y cells overexpressing human amyloid precursor protein (APP) were treated with GLP-1. Western blot analysis was used to assess the effects of GLP-1 on the metabolism of Aβ. Results:Plasma GLP-1 levels were decreased with aging. Plasma GLP-1 levels were lower in AD patients in comparison with healthy older adults. Plasma GLP-1 levels were positively associated with Mini-Mental State Examination scores but negatively associated with plasma pTau181 levels. GLP-1 dose-dependently increased the area fraction of mitochondrial staining in vitro. Furthermore, GLP-1 dose-dependently promoted the α-cleavage of APP, thus reducing the generation of Aβ. Conclusions:GLP-1 has neuroprotective effects in AD, and therefore the decrease in GLP-1 levels during aging might contribute to the development of AD.
Keywords: Aging, Alzheimer’s disease, amyloid-β, glucagon-like peptide-1 (GLP-1), tau protein phosphorylation
