载脂蛋白E基因多态性与阿尔茨海默病和轻度认知功能障碍患者尿阿尔茨海默病相关神经丝蛋白的关系

Correlation between apolipoprotein E gene polymorphism and the urine level of Alzheimer-associated neuronal thread protein in patients with Alzheimer＇s disease and mild cognitive impairment

目的 探讨载脂蛋白E（ApoE）基因多态性与阿尔茨海默病（AD）、轻度认知功能障碍（MCI）患者尿AD相关神经丝蛋白（AD7c-NTP）的关系.方法 选取2016年6月至2017年6月就诊于安徽医科大学第一附属医院神经内科的30例AD患者（AD组）、30例MCI患者（MCI组）、30名性别和年龄相匹配的认知正常者（对照组）为研究对象,使用多种神经心理学量表对所有研究对象进行认知功能评价;采用酶联免疫吸附测定法检测尿AD7c-NTP水平;采用高分辨率熔解曲线法分析ApoE基因型.结果 AD组、MCI组和对照组尿AD7c-NTP含量分别是1.03 （0.80,1.41）、0.69（0.53,0.91）、0.59（0.40,0.66） ng/ml,AD和MCI组与对照组相比AD7c-NTP含量均较高,差异有统计学意义（Z=33.727,P＜0.01）;AD组与MCI组相比AD7c-NTP含量亦明显升高,差异有统计学意义（Z=8.232,P＜0.05）.Spearman秩相关分析显示尿AD7c-NTP含量与MMSE总分、剑桥老年认知检查表-中国修订版（CAMCOG-C）总分呈显著负相关（rMMSE=-0.604,P＜0.01;rCAMCOG-C=-0.486,P＜0.01）,且与CAMCOG-C多个子项目有相关性.受试者工作特征曲线得出当尿AD7c-NTP含量为0.70 ng/ml时,诊断认知损害（包括AD和MCI）敏感度和特异度之和最大,分别为71.7％和83.3％,曲线下面积是0.82（95％ CI0.73-0.90,P＜0.05）.本研究样本中,ApoE基因型有ε2/3、ε3/3、ε3/4、ε4/4,ε4携带者比例在AD组、MCI组、对照组中分别为46.7％ （14/30）、23.3％ （7/30）、23.3％（7/30）.MCI组ε4携带者比非携带者表现出更高的尿AD7c-NTP含量和更低的CAMCOG-C总分,差异均有统计学意义（ZAD7c-NTP=4.857,ZCAMCOG-C=4.284,均P＜0.05）.结论 AD和MCI患者尿AD7c-NTP水平显著升高,尿AD7c-NTP含量越高,认知损害越明显;尤其在携带ApoE ε4等位基因的MCI患者中,表现出尿AD7c-NTP水平更高、认知损害更严重.

Objective To explore the correlation between apolipoprotein E （ApoE） gene polymorphism and urine Alzheimer-associated neuronal thread protein （AD7c-NTP） level in patients with Alzheimer＇s disease （AD） and mild cognitive impairment （MCI）.Methods The cognitive function of 30 AD patients （AD group）,30 MCI patients （MCI group） and 30 normal controls （NC group） was evaluated by neuropsychological batteries like MMSE,the Cambridge Cognitive Examination-Chinese Version （CAMCOG-C）,etc.ELISA was used to test the urine level of AD7c-NTP.The genotypes of ApoE were analyzed by the high-resolution melting assay in blood samples.Results Compared with the NC group （0.59 （0.40,0.66） ng/ml）,the urine level of AD7c-NTP in the AD group （1.03（0.80,1.41） ng/ml） and the MCI group （0.69（0.53,0.91） ng/ml） was increased （Z =33.727,P 〈0.01）.The urine level of AD7c-NTP in the AD group was higher than that in the MCI group （Z =8.232,P 〈 0.05）.The level of AD7c-NTP in urine was negatively correlated with MMSE and CAMCOG-C scores （rMMSE =-0.604,P 〈 0.01;rCAMCOG-C =-0.486,P 〈 0.01）.According to receiver operating characteristic curve,the optimal cutoff point of AD7c-NTP in urine for diagnosis of patients including AD and MCI was 0.70 ng/ml,with sensitivity of 71.7% and specificity of 83.3%,and area under the curve of 0.82 （95% CI 0.73-0.90,P 〈0.05）.There were four genotypes comprising ε2/3,ε3/3,ε3/4 and ε4/4 for ApoE gene.The frequencies of ε4 carriers were 46.7% （14/30）,23.3% （7/30） and 23.3% （7/30） in the AD,MCI and NC groups,respectively.There was a notable increase in urine AD7c-NTP and a significant decrease in CAMCOG-C scores in MCI patients who harbored the ApoE ε4 allele （ZAD7c-NTP =4.857,P 〈 0.05;ZCAMCOG-C =4.284,P 〈0.05）.Conclusions The urine level of AD7c-NTP was significantly increased in AD and MCI patients,the higher the level of AD7c-NTP,the more serious the cognitive impairment.The ε4 carriers exhibited higher urine level of AD7c-NTP,but worse cognitive function compared to ε4 non-carriers in the MCI group.