阿尔茨海默病患者脑脊液SMOC1和OLFML3水平表达及对病情程度的评估价值

Expression of SMOC1 and OLFML3 in Cerebrospinal Fluid of Patients with Alzheimer’s Disease and Its Value in Evaluating the Severity of the Disease

目的探讨阿尔茨海默病(Alzheimer’s disease,AD)患者脑脊液人类SPARC相关模块化钙结合蛋白1(SPARC related modular calcium binding 1,SMOC1)、嗅觉介导素3(olfactomedin-3,OLFM3)水平表达及对病情程度的评估价值。方法选取2020年1月~2023年1月宝鸡市人民医院诊治的AD患者108例(AD组),以同期行腰椎穿刺检查的非认知功能障碍患者60例为对照组。应用酶联免疫吸附实验(ELISA)检测脑脊液SMOC1,OLFML3,β-淀粉样蛋白(Aβ1-40,Aβ1-42)和P-Tau蛋白水平。采用Pearson相关分析探讨脑脊液SMOC1,OLFML3水平与临床指标的相关性。采用Logistic回归分析影响AD患者病情程度的因素。采用受试者工作特征(ROC)曲线研究脑脊液SMOC1,OLFML3对AD病情程度的预测价值。结果AD组脑脊液SMOC1(68.47±11.23 ng/L),OLFML3(110.58±21.39 ng/L),P-Tau(569.07±97.24 ng/L)及CDR评分(1.5分)高于对照组(22.60±4.16 ng/L,36.94±6.97ng/L,182.66±55.37 ng/L,0),脑脊液Aβ1-42(292.23±55.36 ng/L),MoCA评分(7.88±2.05分)、MMSE评分(13.15±2.39分)低于对照组(397.16±60.57ng/L,23.13±4.31分,28.02±4.26分),差异具有统计学意义(t=30.465,25.885,28.313,51.211,11.380,31.038,29.013,均P<0.05)。AD组脑脊液SMOC1,OLFML3分别与P-Tau,CDR评分呈正相关(r=0.703,0.634;0.682,0.713,均P<0.05),与Aβ1-42,MoCA评分、MMSE评分呈负相关(r=-0.662,-0.599;-0.660,-0.588;-0.745,-0.731,均P<0.05)。中重度组AD患者脑脊液SMOC1(89.90±12.17 ng/L),OLFML3(142.46±22.48ng/L),P-Tau(618.83±98.19 ng/L)高于轻度组(56.36±10.52 ng/L,92.56±20.25 ng/L,542.25±95.30 ng/L),而脑脊液Aβ1-42(260.76±53.60 ng/L)低于轻度组(310.02±56.54 ng/L),差异具有统计学意义(t=15.029,11.818,3.968,4.430,均P<0.05)。脑脊液SMOC1(OR=1.451,95%CI:1.120~1.879),OLFML3(OR=1.442,95%CI:1.096~1.897),P-Tau(OR=1.589,95%CI:1.258~2.006)是影响中重度AD发生的危险因素,Aβ1-42(OR=0.628,95%CI:0.493~0.799)是保护因素。脑脊液SMOC1,OLFML3及联合预测对中重度AD患者评估的曲线下面积(95%CI)分别为0.882(0.844~0.929),0.846(0.805~0.877)和0.931(0.883~0.965),联合预测大于各单项指标检测,差异具有统计学意义(Z=3.558,4.172,P=0.004,0.000)。结论AD患者脑脊液SMOC1,OLFML3水平升高,两者与AD患者病情程度有关,脑脊液SMOC1,OLFML3联合检测对中重度AD具有较高的预测价值。

Objective To explore the expression levels of SPARC related modular calcium binding 1(SMOC1)and olfactomedin-3(OLFM3)in the cerebrospinalfluid of Alzheimer’s disease(AD)patients and their value in evaluating the severity of the disease.Methods A total of 108 AD patients(AD group)treated at Baoji People’s Hospital from January 2020 to January 2023 were selected,and 60 non cognitive dysfunction patients who underwent lumbar puncture examination during the same period were selected as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect cerebrospinalfluid SMOC1,OLFML3,β-Amyloid protein(Aβ1-40,Aβ1-42)and P-Tau protein levels.Pearson correlation analysis was conducted to analyze cerebrospinalfluid SMOC1,and OLFML3 levels and their correlation with clinical indicators.Logistic regression was used to analyze the influencing factors of AD severity.Receiver operating characteristic curves were used to analyze the predictive value of cerebrospinalfluid SMOC1 and OLFML3 on the severity of Alzheimer’s disease.Results The levels of SMOC1(68.47±11.23 ng/L),OLFML3(110.58±21.39 ng/L),P-Tau(569.07±97.24 ng/L)and CDR score(1.5 score)in the cerebrospinalfluid of the AD group were higher than those in the control group(22.60±4.16 ng/L,36.94±6.97ng/L,182.66±55.37,0 score),while Aβ1-42(292.23±55.36 ng/L),MoCA score(7.88±2.05 score)and MMSE score(13.15±2.39 score)were lower than those in the control group(397.16±60.57ng/L,23.13±4.31 score,28.02±4.26 score),and the differences were statistically significant(t=30.465,25.885,28.313,51.211,11.380,31.038,29.013,all P<0.05).SMOC1 and OLFML3 of the cerebrospinalfluid in the AD group were positively correlated with P-Tau and CDR score(r=0.703,0.634;0.682,0.713,all P<0.05),but were negatively correlated with Aβ1-42,MoCA score and MMSE score(r=-0.662,-0.599;-0.660,-0.588;-0.745,-0.731,all P<0.05).SMOC1(89.90±12.17 ng/L),OLFML3(142.46±22.48),and P-Tau(618.83±98.19 ng/L)in the cerebrospinalfluid of AD patients in the moderate to severe group were higher than those in the mild group(56.36±10.52 ng/L,92.56±20.25 ng/L,542.25±95.30 ng/L),Aβ1-42 in the moderate to severe group(260.76±53.60 ng/L)was lower than those in the mild group(310.02±56.54 ng/L),and the differences were statistically significant(t=15.029,11.818,3.968,4.430,all P<0.05).SMOC1(OR=1.451,95%CI:1.120~1.879),OLFML3(OR=1.442,95%CI:1.096~1.897)and P-Tau(OR=1.589,95%CI:1.258~2.006)in cerebrospinalfluid were risk factors for moderate to severe cognitive impairment in AD patients,while Aβ1-42 was a protective factor.The AUC(95%CI)of SMOC1,OLFML3 in cerebrospinalfluid,and their combinative forecasting evaluating moderate to severe AD patients were 0.882(0.844~0.929),0.846(0.805~0.877)and 0.931(0.883~0.965),respectively,and their combinative forecasting was higher than two individual indicators(Z=3.558,4.172,P=0.004,0.000).Conclusion The levels of SMOC1 and OLFML3 in cerebrospinal fluid are elevated in AD patients,which are related to the severity of AD.The combinative forecasting of the two has high predictive value for moderate to severe AD.