脑脊液突触体相关蛋白25在阿尔茨海默病中的作用及其与相关认知域的关系OA

Objective To investigate the role of cerebrospinal fluid(CSF)synaptosomal associated protein 25(SNAP-25)in the diagnosis and prediction of dementia progression and its association with the relevant cognitive domains by cross-sectional and longitudinal observations.Methods A total of 146 participants with CSF SNAP-25 data from Alzheimer's Disease Neuroimaging Initiative(ADNI)database included 55 cognitively unimpaired(CU)subjects,75 mild cognitive impairment(MCI)subjects,and 16 subjects with dementia.Among 75 MCI individuals with at least 6 months of follow-up clinical assessments,we found 42 remained stable(stable MCI,sMCI),whereas 33 progressed to dementia(progressive MCI,pMCI).Non-parametric tests were used to compare the inter-group differences in CSF SNAP-25 levels.The value of CSF SNAP-25 in diagnosing AD and predicting dementia progression was evaluated by receiver operating characteristics(ROC)curve.Kaplan-Meier survival curve was used to analyze the value of CSF SNAP-25 in predicting the risk of MCI progression to dementia.Finally,the optimal cut-off value of ROC curve for predicting the transformation of MCI to dementia with CSF SNAP-25 was the cut-off value,and the study population was divided into low level group(n=77)and high level group(n=69).Non-parametric test was used to compare the differences of MMSE score,ADAS-Cog score,RAVLT score and MTT-B score between the high level group and the low level group.Spearman correlation analysis was used to analyze the correlation between baseline CSF SNAP-25 level and baseline MMSE score,ADAS-cog score,RAVLT score,TMT-B score and the annual rate of change(△MMSE,△ ADAS,△RAVLT,△TMT-B).Results The CSF SNAP-25 levels was higher in dementia individuals and MCI individuals compared with CU controls(P=0.032,0.005).In addition,further follow-up analysis of the MCI group showed that the level of CSF SNAP-25 in pMCI group was significantly higher than that in sMCI group(P=0.015).ROC curve analysis showed that the AUC of CSF SNAP-25 predicting MCI progression to dementia was 0.66(P=0.019,95%CI:0.53-0.78).Kaplan-Meier survival analysis showed that the risk of progression to dementia in MCI subjects with high CSF SNAP-25 levels was 2.89 times greater than in MCI subjects with low CSF SNAP-25 levels(P=0.015,95%CI:1.38-6.03).Further analysis of different CSF SNAP-25 level groups showed that the baseline MMSE score of high level group was significantly lower than that of low level group(P=0.007),the baseline ADAS-Cog score of high level group was significantly higher than that of low level group(P=0.013),while there was no significant difference in baseline RAVLT score and baseline MTT-B score between the two groups(P>0.05).The decrease of annual MMSE score and annual RAVLT score of high level group was significantly higher than that of low level group(P<0.001,P=0.005),the increase of annual ADAS-Cog score and annual MTT-B score of high level group was significantly higher than that of low level group(P=0.027,0.002).Spearman correlation analysis showed that the baseline CSF SNAP-25 level was negatively correlated with the baseline MMSE score(rs=-0.27,P=0.001,n=146)and the baseline RAVLT score(rs=-0.25,P=0.003,n=146),positively correlated with the baseline ADAS-Cog score(rs=0.26,P=0.002,n=146),and not correlated with the baseline TMT-B score(rs=0.05,P=0.511,n=145).The baseline cerebrospinal fluid SNAP-25 concentration was negatively correlated with △MMSE(rs=-0.29,P=0.001,n=119),△ADAS(rs=-0.27,P=0.009,n=122),and △RAVLT(rs=-0.22,P=0.017,n=119),and positively correlated with △ TMT-B(rs=0.28,P=0.002,n=119).Conclusion CSF SNAP-25 levels increase with disease severity and are associated with the risk of MCI progression to dementia.In addition,the level of CSF SNAP-25 was correlated with the degree of impairment of overall cognitive function,memory function and executive function.