脑脊液生物标志物在特发性正常压力脑积水中的应用

Application of cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus

目的:探讨特发性正常压力脑积水(iNPH)的病理生理学特点,并评估脑脊液(CSF)生物标志物的诊断和预后价值。方法:收集2016年10月-2018年6月在我院行脑室腹腔分流术的iNPH患者18例。获取手术前(术前组)及手术后6个月(术后组)的脑脊液;同时获取12例健康老年人(对照组)的脑脊液。运用酶联免疫吸附实验(ELISA)测定脑脊液生物标志物神经丝轻链蛋白(NFL),淀粉样蛋白-β42(Aβ42),总tau蛋白(T-tau),磷酸化tau蛋白(P-tau),水通道蛋白1(AQP1)和白蛋白(Albumin)的含量。评估iNPH患者术前及术后6个月主要临床症状。结果:18例iNPH患者脑室腹腔分流术后6个月复查时,13例(72%)iNPH评分有所改善。iNPH患者术前组脑脊液中NFL和AQP1高于对照组,比值分别为1.53和1.48(P<0.05);而T-tau、P-tau和Aβ42低于对照组,比值分别为0.64,0.68和0.48(P<0.05);两组间白蛋白水平无明显差异(P>0.05)。iNPH患者术后组脑脊液中NFL、Aβ42、P-tau、白蛋白水平较术前组增加,对应比值为0.72,0.62,0.47和0.48(P<0.05);然而AQP1和T-tau水平较术前组下降,对应比值为2.01和1.15(P<0.05)。结论:特发性正常压力脑积水可引起脑室周围代谢水平降低和轴突变性,但没有主要的皮质损伤。

Objective:This study aimed to explore the pathophysiology of idiopathic normal pressure hydrocephalus(iNPH)and to evaluate the diagnostic and prognostic value of CSF biomarkers.Methods:18 patients with iNPH who underwent ventriculoperitoneal shunt in our hospital from October 2016 to June 2018 were enrolled.Cerebrospinal fluid(CSF)was obtained before surgery(preoperative group)and 6 months after surgery(postoperative group),and CSF was collected from 12 healthy elderly individuals(control group).The levels of CSF biomarkers NFL,Aβ42,T-tau,P-tau,AQP1,and Albumin were analyzed by enzyme-linked immunosorbent assay(ELISA).The clinical symptoms of iNPH patients before and 6 months after surgery were evaluated.Results:At 6 months after ventriculoperitoneal shunt surgery,13(72%)of the 18 iNPH patients had an improved iNPH score.The levels of NFL and AQP1 in the iNPH preoperative group were higher than those in the control group,the ratios were 1.53 and 1.48,respectively(P<0.05);while the levels of T-tau,P-tau and Aβ42 were lower than the control group,the ratios were 0.64,0.68 and 0.48,respectively(P<0.05);there was no significant difference in albumin between the two groups(P>0.05).The levels of NFL,Aβ42,P-tau and albumin in the iNPH postoperative group increased compared with the iNPH preoperative group,and the corresponding ratios were 0.72,0.62,0.47 and 0.48(P<0.05).However,the levels of AQP1 and T-tau were decreased compared with the preoperative group,and the corresponding ratios were 2.01 and 1.15(P<0.05).Conclusion:The pathophysiology of iNPH is characterized by reduced periventricular metabolism and axonal degeneration but no major cortical damage.