脑脊液骨桥蛋白与阿尔茨海默病的关系

ASSOCIATION BETWEEN CEREBROSPINAL FLUID OSTEOPONTIN AND ALZHEIMER’S DISEASE

目的评估骨桥蛋白(OPN)是否可以作为阿尔茨海默病(AD)的早期生物标志物。方法根据临床诊断和生物标志物水平,将纳入人群分为AD组、轻度认知功能障碍(MCI)+β-淀粉样蛋白(Aβ)阳性组(MCI Aβ^(+)组)、MCI+Aβ阴性组(MCI Aβ^(-)组)、认知正常(CN)+Aβ阳性组(CN Aβ^(+)组)及CN+Aβ阴性组(CN Aβ^(-)组),利用协方差分析比较OPN的组间差异。应用相关性分析检验非痴呆人群(包括MCI及CN)脑脊液(CSF)中OPN与AD相关生物标志物及海马体积的相关性。结果MCI Aβ^(+)组和AD组病人CSF中OPN水平均显著高于CN Aβ^(-)组(H=15.473,P<0.01)。在横向分析中,非痴呆人群CSF中OPN水平与Aβ_(42)水平呈负相关(r=-0.265,P<0.01),与总tau(t-tau)及磷酸化tau(p-tau)水平呈正相关(r=0.527、0.309,P<0.01)。在纵向分析中,非痴呆人群CSF中OPN水平与Aβ_(42)及海马体积的变化率呈负相关(r=-0.129、-0.151,P<0.05),与t-tau和p-tau的变化率呈正相关(r=0.315、0.271,P<0.01)。结论CSF OPN水平在AD早期阶段升高,并且与AD早期病理改变相关,是AD潜在的早期生物标志物。

Objective To investigate whether osteopontin(OPN)can be used as an early biomarker for Alzheimer’s di-sease(AD).Methods Based on clinical diagnosis and levels of biomarkers,the subjects enrolled were divided into AD group,mild cognitive impairment(MCI)+β-amyloid(Aβ)-positive group(MCI Aβ^(+) group),MCI+Aβ-negative group(MCI Aβ^(-) group),cognitive normal(CN)+Aβ-positive group(CN Aβ^(+) group),and CN+Aβ-negative group(CN Aβ-group),and a cova-riance analysis was used to compare the difference in OPN between groups.A correlation analysis was used to investigate the correlation of OPN in cerebrospinal fluid(CSF)with AD-related biomarkers and hippocampal volume in the non-dementia population(the population with MCI or CN).Results The MCI Aβ^(+) group and the AD group had a significantly higher level of OPN in CSF than the CN Aβ-group(H=15.473,P<0.01).In the cross-sectional analysis of the non-dementia population,OPN level in CSF was negatively correlated with Aβ_(42) level(r=-0.265,P<0.01)and positively correlated with the levels of total tau(t-tau)and phosphorylated tau(p-tau)(r=0.527,0.309;P<0.01).In the longitudinal analysis of the non-dementia population,OPN level in CSF was negatively correlated with the rates of change of Aβ_(42) and hippocampal volume(r=-0.129,-0.151;P<0.05)and was positively correlated with the rates of change in t-tau and p-tau(r=0.315,0.271;P<0.01).Conclusion There is an increase in the level of OPN in CSF in the early stage of AD,which is associated with early pathological changes of AD,and therefore,it can be used as a potential early biomarker for AD.