【摘要】 目的 分析脑脊液突触小体相关蛋白-25(SNAP-25)与长链非编码RNA核富集转录本1(NEAT1)联合检测对阿尔茨海默病患者认知障碍程度以及病情进展的评估价值。方法 选取650例阿尔茨海默病患者作为研究对象，并根据患者的认知功能分为正常组(n=162)、轻度认知障碍组(n=380)和痴呆组(n=108)。分析脑脊液SNAP-25和NEAT1水平与简易精神状态检查量表(MMSE)评分、临床痴呆评定量表(CDR)评分的相关性。根据轻度认知障碍组患者是否进展至痴呆(随访6个月),分为病情进展组(进展至痴呆)和病情稳定组(未进展至痴呆)。比较各组患者脑脊液SNAP-25和NEAT1水平。采用受试者工作特征(ROC)曲线分析脑脊液SNAP-25联合NEAT1对痴呆的诊断价值及对轻度认知障碍进展至痴呆的预测效能。结果 轻度认知障碍组和痴呆组脑脊液的SNAP-25和NEAT1 mRNA水平高于正常组，痴呆组的脑脊液SNAP-25和NEAT1 mRNA水平高于轻度认知障碍组，差异有统计学意义(P<0.05)。轻度认知障碍组和痴呆组患者的脑脊液SNAP-25和NEAT1 mRNA水平与MMSE评分呈负相关(P<0.05),与CDR评分呈正相关(P<0.05)。轻度认知障碍组有133例患者病情由轻度认知障碍进展至痴呆。病情进展组患者的脑脊液SNAP-25和NEAT1 mRNA水平高于病情稳定组，差异有统计学意义(P<0.05)。ROC曲线分析显示，脑脊液SNAP-25联合NEAT1诊断痴呆的敏感度为89.63%,特异度为54.08%,曲线下面积(AUC)为0.884;脑脊液SNAP-25联合NEAT1预测轻度认知障碍进展至痴呆的敏感度为83.41%,特异度为56.70%, AUC为0.867。结论 脑脊液中SNAP-25和NEAT1的水平会随阿尔茨海默病患者认知障碍程度的加重而显著升高。SNAP-25与NEAT1联合检测对痴呆的诊断效能以及轻度认知障碍进展至痴呆的预测价值较高。更多还原

【Abstract】 Objective To evaluate value of combined detection of cerebrospinal fluid synaptosomal-associated protein 25(SNAP-25) and long non-coding RNA nuclear-enriched transcript 1(NEAT1) in assessing cognitive impairment severity and disease progression in patients with Alzheimer’s disease.Methods A total of 650 patients with Alzheimer’s disease were selected as research subjects and divided into normal group(n=162),mild cognitive impairment group(n=380) and dementia group(n=108) according to their cognitive function.The correlations of the levels of SNAP-25 and NEAT1 in cerebrospinal fluid with the scores of Mini-Mental State Examination(MMSE) and Clinical Dementia Rating Scale(CDR) were analyzed.According to whether the patients in the mild cognitive impairment group progressed to dementia(followed up for 6 months),they were divided into disease progression group(progressed to dementia) and stable disease group(did not progress to dementia).The levels of SNAP-25 and NEAT1 in cerebrospinal fluid of patients in each group were compared.The receiver operating characteristic(ROC) curve was used to analyze the diagnostic value of cerebrospinal fluid SNAP-25 combined with NEAT1 for dementia and its predictive efficacy for the progression of mild cognitive impairment to dementia.Results The levels of SNAP-25 and NEAT1 mRNA in cerebrospinal fluid in the mild cognitive impairment group and the dementia group were significantly higher than those in the normal group;the levels of cerebrospinal fluid SNAP-25and NEAT1 mRNA in the dementia group were significantly higher than those in the mild cognitive impairment group(P <0.05).The levels of cerebrospinal fluid SNAP-25 and NEAT1 mRNA in patients of the mild cognitive impairment group and the dementia group were negatively correlated with the MMSE score(P <0.05),and positively correlated with the CDR score(P <0.05).In the mild cognitive impairment group,133 patients’ conditions progressed from mild cognitive impairment to dementia.The levels of cerebrospinal fluid SNAP-25 and NEAT1 mRNA in the disease progression group were significantly higher than those in the stable disease group(P <0.05).ROC curve analysis showed that the sensitivity of cerebrospinal fluid SNAP-25 combined with NEAT1 in diagnosing dementia was 89.63%,the specificity was 54.08%,and the area under the curve(AUC) was0.884.The sensitivity of cerebrospinal fluid SNAP-25 combined with NEAT1 in predicting the progression of mild cognitive impairment to dementia was 83.41%,the specificity was 56.70%,and the AUC was 0.867.Conclusion The levels of SNAP-25 and NEAT1 in cerebrospinal fluid increase significantly with the aggravation of cognitive impairment in patients with Alzheimer’s disease.The combined detection of SNAP-25 and NEAT1 has relatively high diagnostic efficacy for dementia and predictive value for the progression from mild cognitive impairment to dementia.更多还原