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目的:研究阿尔茨海默病(Alzheimer\'s disease，AD)患者血液中mRNA N6-甲基腺苷甲基化水平以及甲基转移酶3(methyltransferase-like 3，METTL3)和去甲基化酶脂肪与肥胖相关基因(fat mass and obesity-associated gene，FTO)蛋白的变化情况。方法:选取2020年1月至2021年6月在济宁医学院附属医院神经内科门诊及住院就诊的40例AD患者作为患者组，另选40例健康志愿者作为对照组。采集所有被试血样，提取血浆和外周血单个核细胞，采用酶联免疫吸附测定(enzyme linked immunosorbent assay，ELISA)、蛋白质印迹(Western blot，WB)、实时荧光定量PCR(quantitative real-time PCR，qRT-PCR)以及m6A甲基化定量等实验对METTL3、FTO和m6A甲基化水平进行检测，所得数据采用SPSS 23.0统计软件进行n t检验。n 结果:两组被试血浆METTL3、FTO蛋白浓度比较，AD组均小于对照组[METTL3：(22.33±3.01)ng/mL，(25.63±1.70)ng/mL，n t＝6.055，n P<0.01；FTO：(63.51±4.95)pg/mL，(69.60±4.60)pg/mL，n t＝5.704，n P<0.01]。两组外周血单个核细胞METTL3、FTO蛋白条带灰度值比较，AD组均小于对照组[METTL3：(0.399 5±0.028 7)，(0.676 6±0.053 3)，n t＝7.935，n P＝0.001；FTO：(0.439 4±0.017 8)，(0.782 6±0.087 6)，n t＝6.652，n P＝0.003]。两组外周血单个核细胞RNA中METTL3、FTO表达水平比较，AD组均小于对照组[METTL3：(0.387 8±0.020 3)，(1.010 0±0.177 0)，n t＝6.041，n P＝0.004；FTO：(0.442 8±0.037 1)，(1.003 0±0.090 4)，n t＝9.931，n P＝0.001]。两组外周血单个核细胞RNA中m6A水平比较，AD组小于对照组[(0.000 571±0.000 167)%，(0.002 514±0.001 284)%，n t＝6.041，n P＝0.004]。n 结论:AD患者血浆和外周血单个核细胞中METTL3、FTO和m6A甲基化水平均下降，表明mRNA N6-甲基腺苷甲基化与AD的存在一定的关联。“,”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 n t-test.n 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, n t=6.055, n P<0.01; FTO: (63.51±4.95)pg/mL, (69.60±4.60)pg/mL, (n t=5.704, n 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,n t=7.935, n P=0.001; FTO: 0.439 4±0.017 8, 0.782 6±0.087 6, n t=6.652, n 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, n t=6.041, n P=0.004; FTO: 0.442 8±0.037 1, 1.003 0±0.090 4, n t=9.931, n 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)%, n t=6.041, n P=0.004).n 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.