生物学标志物联合同型半胱氨酸和ApoB/LDL-C检测在阿尔茨海默病早期鉴别诊断中的应用

Application of biological markers combined with homocysteine and ApoB/LDL-C in early differential diagnosis of Alzheimer's disease

目的 探讨血液生物学标志物联合同型半胱氨酸(Hcy)和载脂蛋白B/低密度脂蛋白胆固醇(Apo B/LDL-C)检测在阿尔茨海默病(AD)早期鉴别诊断中的应用。方法 选择2019年1月—2021年12月在徐州医科大学第二附属医院神经内科收治住院的100例主诉存在记忆力下降和(或)其他认知域损伤患者作为研究对象,根据简易智能精神状态检查量表(MMSE)及相应诊断标准分为轻度认知障碍(MCI)组(40例)、早期AD组(30例)和早期血管性痴呆(Va D)组(30例);另外选择同期50名健康体检者作为健康对照(NC)组。所有受检者均检测常见血液指标[Hcy、ApoB、LDL-C、β-淀粉样蛋白1-42(Aβ1-42)、血清磷酸化tau-181蛋白(P-tau-181)],比较各组上述指标的差异。绘制受试者工作特征曲线(ROC曲线)并计算ROC曲线下面积(AUC),比较各指标单独与联合检测在AD早期鉴别诊断中的效能。结果 MCI组和早期AD组的Hcy、Aβ1-42、P-tau-181水平均明显高于早期VaD组和NC组[Hcy(μmol/L):17.51±4.21、19.78±6.86比14.27±3.62、14.21±2.31,Aβ1-42(ng/L):138.57±42.12、109.42±21.40比91.51±13.67、90.82±15.31,P-tau-181(ng/L):109.72±28.93、138.54±36.36比89.67±19.55、82.76±15.68,均P<0.05]。MCI组的Apo B/LDL-C和Aβ1-42水平均明显高于早期AD组,Hcy和P-tau-181均明显低于早期AD组[ApoB/LDL-C:0.32±0.03比0.30±0.04,Aβ1-42(ng/L):138.57±42.12比109.42±21.40,Hcy(μmol/L):17.51±4.21比19.78±6.86,P-tau-181(ng/L):109.72±28.93比138.54±36.36,均P<0.05];早期Va D组患者的Apo B/LDL-C水平明显高于早期AD组和NC组(0.35±0.06比0.30±0.04、0.32±0.05,均P<0.05)。Hcy、Aβ1-42和P-tau-181联合检测诊断MCI的AUC最高,为0.973[95%可信区间(95%CI)为0.946~0.999];Hcy、Aβ1-42和P-tau-181联合检测诊断AD的AUC最高,为0.957(95%CI为0.906~1.000);Hcy、Aβ1-42、Apo B/LDL-C和P-tau-181联合检测鉴别AD和Va D的AUC最高,为0.941(95%CI为0.885~0.997)。结论 Hcy、Aβ1-42、P-tau-181在AD相关疾病的早期鉴别诊断中均有一定价值,ApoB/LDL-C可成为预测VaD患者认知损伤程度的首选指标。

Objective To investigate the application of blood biological markers combined with homocysteine(Hcy)and apolipoprotein B/low-density lipoprotein cholesterol(ApoB/LDL-C)in early differentiation and diagnosis of Alzheimer's disease(AD).Methods The 100 patients who complained of memory loss and(or)other cognitive domain impairment and were hospitalized in neurology department of the Second Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2021 were selected as research objects.According to the mini-mental state examination(MMSE)and the corresponding diagnostic criteria,the patients were divided into mild cognitive impairment(MCI)group(40 cases),early AD group(30 cases)and early vascular dementia(VaD)group(30 cases).Other 50 healthy subjects at the same period were selected as normal control(NC)group.All participants were tested for common blood indicators[Hcy,ApoB,LDL-C,β-amyloid protein 1-42(Aβ1-42),serum phosphorylated tau-181 protein(P-tau-181)],and the differences of each index in each group were compared.The receiver operator characteristic(ROC)curve was drawn and the area under the ROC curve(AUC)was calculated to compare the efficacy of each index alone and combined detection in the early differential diagnosis of AD.Results The levels of Hcy,Aβ1-42 and P-tau-181 in MCI group and early AD group were higher than those in early VaD group and NC group[Hcy(μmol/L):17.51±4.21,19.78±6.86 vs.14.27±3.62,14.21±2.31,Aβ1-42(ng/L):138.57±42.12,109.42±21.40 vs.91.51±13.67,90.82±15.31,P-tau-181(ng/L):109.72±28.93,138.54±36.36 vs.89.67±19.55,82.76±15.68,all P<0.05].The levels of ApoB/LDL-C and Aβ1-42 in MCI group were higher than those in early AD group,and the levels of Hcy and P-tau-181 were lower than those in early AD group[ApoB/LDL-C:0.32±0.03 vs.0.30±0.04,Aβ1-42(ng/L):138.57±42.12 vs.109.42±21.40,Hcy(μmol/L):17.51±4.21 vs.19.78±6.86,P-tau-181(ng/L):109.72±28.93 vs.138.54±36.36,all P<0.05].The level of ApoB/LDL-C in early VaD group was higher than those in early AD group and NC group(0.35±0.06 vs.0.30±0.04,0.32±0.05,both P<0.05).The combination of Hcy,Aβ1-42 and P-tau-181 for the diagnosis of MCI had the highest AUC,which was 0.973[95%confidence interval(95%CI)was 0.946-0.999].The combination of Hcy,Aβ1-42 and P-tau-181 had the highest AUC for the diagnosis of AD,which was 0.957(95%CI was 0.906-1.000).The combination of Hcy,Aβ1-42,ApoB/LDL-C and P-tau-181 had the highest AUC for identification of AD and VaD,which was 0.941(95%CI was 0.885-0.997).Conclusions The detection of Hcy,Aβ1-42,P-tau-181 and other indicators has certain value in the early diagnosis of AD-related diseases.ApoB/LDL-C has important clinical significance for the early differential diagnosis of AD and VaD.ApoB/LDL-C ratio could be used as the first choice to predict the degree of cognitive impairment in VaD patients.