Correlation Between Apolipoprotein E Gene Polymorphism And The Urine Level Of AD7C-NTP In Patients With Alzheimer's Disease And Mild Cognitive Impairment

Objectives 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?.Materials and methods Ninety subjects were recruited in the First Affiliated Hospital,Anhui Medical University from June 2016 to June 2017 and they were divided into AD group?n=30?,MCI group?n=30?and normal cognitive?NC?group?n=30?.The cognitive function of all subjects was evaluated by neuropsychological batteries like MMSE,the Cambridge Cognitive Examination-Chinese Version?CAMCOG-C?,etc.5-10 milliliters of urine samples were collected from the patients'first morning urination,and all the urine samples were stored in the refrigerator at 4?immediately and detected during 1 week.The levels of AD7c-NTP in the urine were detected by double antibody sandwich enzyme-linked immunosorbent assay?ELISA?.Two milliliters of peripheral venous blood were collected in EDTA-containing blood vessels and were refrigerated at-20?before DNA extraction.Genomic DNA was extracted by a universal column genomic extraction kit.The extracted genomic DNA was stored in a-80?refrigerator.The genotypes of ApoE were analyzed by the high-resolution melting curve?HRM?assay.Result The scores of MMSE and CAMCOG-C in AD and MCI are lower than that of NC group(Z_MMSE=72.890,P=0.000;Z_CAMCOG-C=71.230,P=0.000).Compared with the NC group,the urine level of AD7c-NTP in the AD and MCI groups was increased?Z=33.727,P<0.01?.The urine level of AD7c-NTP in the AD group was higher than 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(r _MMSE=–0.604,P<0.01;r_CAMCOG-C=–0.486,P<0.01),and negatively correlated with orientation,language,etc,in CAMCOG-C subgroup?P<0.05?.According to receiver operating characteristic?ROC?curve,the optimal cutoff point of AD7c-NTP in urine for diagnosis of patients including AD and MCI was 0.7 ng/ml,with sensitivity of 71.7%and specificity of 83.3%,and area under the curve was 0.82?95%CI:0.73–0.90,P<0.05?.There were four genotypes comprising?2/3,?3/3,?3/4 and?4/4 for ApoE gene.The frequencies of?4 carriers were46.7%,23.3%and 23.3%in 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?4 allele(Z_AD7c-NTP=4.857,P<0.05;Z_CAMCOG-C=4.284,P<0.05).Conclusion The urine level of AD7c-NTP was significantly increased in AD and MCI patients,the more serious the cognitive impairment,the higher the level of AD7c-NTP.The proportion of carriers of ApoE?4 allele in AD group and MCI group was more than that in NC group.The?4 carriers exhibited higher urine level of AD7c-NTP,but worse cognitive function compared to?4 non-carriers in the MCI group.