帕金森病患者血浆DYRK1A tau p-tau水平与认知功能障碍的关联性研究

A study on the correlation between plasma DYRK1A,tau,p-tau levels and cognitive dysfunction in patients with Parkinson′s disease

目的 探讨帕金森病(PD)患者血浆双底物特异性酪氨酸磷酸化调节激酶1A(DYRK1A)、tau、磷酸化tau(p-tau)水平与认知功能障碍的关联性及对认知功能障碍的诊断价值。方法 纳入87例PD患者,收集其一般资料,根据蒙特利尔认知评估(MoCA)量表评分将其分为认知功能正常组(PD-NC组,17例)、轻度认知障碍组(PD-MCI组,30例)和痴呆组(PDD组,40例)。采用酶联免疫吸附试验法检测研究对象血浆DYRK1A、tau、p-tau水平,比较不同认知功能组中血浆DYRK1A、tau、p-tau水平的差异,分析这三个指标对PD痴呆的诊断效能。结果 PD-NC组的血浆DYRK1A水平显著低于PD-MCI组(P=0.033)及PDD组(P=0.005),而PD-MCI组与PDD组比较差异无统计学意义(P=0.468)。PD-NC组的血浆tau水平显著低于PDD组(P=0.006),但PD-NC组与PD-MCI组比较以及PD-MCI组与PDD组比较差异无统计学意义(P>0.05)。三组间p-tau水平比较差异无统计学意义(P>0.05)。ROC曲线结果显示tau蛋白具有诊断PD痴呆的应用价值(AUC=0.658,P=0.012),其最佳截断值为175.88 pg/ml,对应的灵敏度为75.00%,特异度为55.30%,联合指标DYRK1A、p-tau或三指标联合,均可提高诊断效能,其中以DYRK1A+tau+p-tau三指标联合的诊断效能最高(AUC=0.688)。单一指标DYRK1A、p-tau未显著出诊断PD痴呆的应用价值(P>0.05)。结论 不同认知功能障碍的PD患者血浆DYRK1A、tau水平存在差异,tau水平对PD痴呆有诊断效能,联合检测可一定程度上提高诊断的敏感性。

Objective To explore the correlation between plasma DYRK1A,tau,p-tau levels and cognitive dysfunction in patients with Parkinson′s disease(PD)and their diagnostic value of cognitive dysfunction in PD.Methods Eighty-seven patients with PD were included as the research subjects,and their general data were collected.The patients were divided into normal cognitive function group(PD-NC group,17 cases),mild cognitive impairment group(PD-MCI group,30 cases)and dementia group(PDD group,40 cases)according to their different Montreal Cognitive Assessment(MoCA)Scale scores.Enzyme-linked immunosorbent assay was used to detect the levels of DYRK1A,tau and p-tau in the plasma of the subjects.The differences in the levels of DYRK1A,tau and p-tau were compared among different cognitive function groups,and the diagnostic efficacy of these three indicators for PD dementia was analyzed.Results The level of plasma DYRK1A in the PD-NC group was significantly lower than that in the PD-MCI group(P=0.033)and the PDD group(P=0.005),but there was no significant difference between the PD-MCI group and the PDD group(P=0.468).The tau level in the PD-NC group was significantly lower than that in the PDD group(P=0.006),but there was no significant difference between the PD-NC group and the PD-MCI group as well as between the PD-MCI group and the PDD group(P>0.05).There was no significant difference in p-tau level among the three groups(P>0.05).The results of receiver operating characteristic(ROC)curve showed that tau protein had application value in diagnosis of PD dementia[the area under the curve(AUC)=0.658,P=0.012],and its optimum cut-off value was 175.88 pg/ml,with a corresponding sensitivity being 75.00%and a specificity being 55.30%.The tau protein combined with DYRK1A or p-tau,or the combination of the three indicators could improve the diagnostic efficacy,among which the combination of the three indicators of DYRK1A+tau+p-tau had the highest diagnostic efficacy(AUC=0.688).The single indicator DYRK1A or p-tau had no significant application value in diagnosis of PD dementia(P>0.05).Conclusion There are significant differences in plasma DYRK1A and tau levels in PD patients with different cognitive dysfunction.Tau levels have diagnostic efficacy for PD dementia,and combined detections can improve the sensitivity of the diagnosis to some extent.