GENETIC POLYMORPHISM OF SERUM EXOSOME-ASSOCIATED MICRORNAS IN PATIENTS WITH ALZHEIMER’S DISEASE

Weidong Su¹, Zhoufan Wang³, Yan Zhu³, Yang Zhang², Ling Zhu³, Lijun Li², Mingjie Xia⁴, Li Li^{2, *}

¹Clinical College, Changsha Health Vocational College, Changsha, 410600, China - ²Obstetrics and Gynecology Department, The fourth hospital of Changsha, Changsha, 410006, China - ³Neurology Department, Xiangtan Central Hospital, Xiangtan, 411100, China - ⁴Department of Cardiovascular Medicine, Shaoyang University Affiliated Second Hospital, Shaoyang, 422000, China

Objective: This research aims to study the genetic polymorphism of serum exosome-associated MicroRNAs (MicroRNAs, miRNA) in patients with Alzheimer’s disease (AD). 

Methods: From June 2018 to June 2020, 120 AD patients were treated in the Affiliated Hospital of Medical University, including 63 males and 57 females, aged 50 to 85 years, with an average age of 69.22±5.76 years. 120 healthy subjects served as the control group, including 62 males and 58 females, aged 48 to 86 years, with an average age of 68.53±6.59 years. After fasting for 12 hours, peripheral blood was collected from each patient. Total Exosome Isolation Kit was used to isolate exosomes. Genotyping was carried out by PCR. The expression levels of miR-23a-3p and miR-197-5p genes were detected by real-time PCR. Cognitive function was assessed through MMSE. The level of IL-6 was detected by Western blot. 

Results: There were no statistically significant differences between the control group and the AD group in age, gender, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (total cholesterol, TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides (TG) (P>0.05). Compared with the control group, the frequency of AA genotype and A allele decreased in the AD group (P<0.05), and the frequency of AG genotype, GG genotype and G allele increased (P<0.05). Compared with the control group, the frequency of TT genotype and T allele decreased in the AD group (P<0.05), and the frequency of TC genotype, TT genotype and T allele increased (P<0.05). Compared with the control group, the expression levels of miR-23a-3p genotypes AA and AG+GG and miR-197-5p genotypes TT and TC+CC increased. The MMSE scores decreased, and the level of IL-6 in the AD group All increased (P<0.05). In the control group, miR-23a-3p genotypes AA and AG+GG, miR-197-5p genotypes TT and TC+CC gene expression levels, MMSE scores and IL-6 levels did not differ (P>0.05). In the AD group, the expression level of miR-23a-3p genotype AG+GG was higher than that of AA and the expression level of miR-197-5p genotype TC+CC was higher than that of TT gene. Both of their MMSE scores were lower, and IL-6 levels were higher (P<0.05). 

Conclusion: The polymorphism of miR-23a-3p and miR-197-5p changed the expression levels of miR-23a-3p and miR-197-5p. The change may regulate the inflammatory response in the brain of AD patient and further aggravate the susceptibility to AD. MiR-23a-3p genotype AG+GG and miR-197-5p genotype TC+CC were associated with an increased risk of cognitive decline in AD patients.