Changes of mRNA N6-methyladenosine methylation in blood of patients with Alzheimer's disease / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To explore the changes of mRNA N6-methyladenosine methylation level and methyltransferase-like 3 (METTL3) and demethylase fat mass and obesity-associated (FTO) in the blood of patients with Alzheimer's disease (AD) compared with normal controls.Methods:From January 2020 to June 2021, totally 40 AD patients treated in the outpatient and inpatient department of Neurology of the Affiliated Hospital of Jining Medical University were selected as the patient group, and 40 healthy volunteers as the control group. The blood samples were collected to extract plasma and peripheral blood mononuclear cells for enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real-time PCR (qPCR) and m6A methylation quantification experiments respectively to detect the methylation levels of METTL3, FTO and m6A. The data were analyzed by SPSS 23.0 statistical software for t-test. Results:The plasma concentrations of METTL3 and FTO protein in AD group were lower than those in control group (METTL3 (22.33±3.01)ng/mL, (25.63±1.70)ng/mL, t=6.055, P<0.01; FTO (63.51±4.95)pg/mL, (69.60±4.60)pg/mL, ( t=5.704, P<0.01). The band gray values of METTL3 and FTO protein in blood cells in AD group were lower than those in control group (METTL3 0.399 5±0.028 7, 0.676 6±0.053 3, t=7.935, P=0.001; FTO 0.439 4±0.017 8, 0.782 6±0.087 6, t=6.652, P=0.003). The expression levels of METTL3 and FTO in blood cell RNA in AD group were lower than those in control group (METTL3 0.387 8±0.020 3, 1.010 0±0.177 0, t=6.041, P=0.004; FTO 0.442 8±0.037 1, 1.003 0±0.090 4, t=9.931, P=0.001). The levels of m6A in blood cell RNA in AD group were lower than those in control group((0.000 571±0.000 167)%, (0.002 514±0.001 284)%, t=6.041, P=0.004). Conclusion:The levels of METL3, FTO and m6A methylation are down-regulated in the plasma and peripheral blood mononuclear cells of patients with AD, indicating that there is a certain association between mRNA N6-methyladenosine methylation and AD.