Abstract: Objective　To evaluate the predictive value of osteopontin（OPN） and inflammatory cytokines in the progression of mild cognitive impairment （MCI） to Alzheimer's disease（AD）．Methods　Prospective analysis of 60 patients with MCI and 60 patients with non-inflammatory neuropathy （OND） matched by age and sex admitted to Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from June 2015 to June 2017 was carried out.The clinical data were collected and condition assessment evaluated by MMSE score.Enzyme linked immunosorbent assay （ELISA） was used to measure the levels of OPN in cerebrospinal fluid （CSF） and serum，interleukin（IL）-1β，IL-6，IL-17A，transforming growth factor （TGF）-β1 and tumor necrosis factor （TNF）-α.All patients were followed up for 1 year.According to whether the disease progressed to AD，subjects were divided into AD group，no-progression group and OND group.Serum OPN level and inflammatory factors were measured again in patients of AD group during follow-up.Results　There were 23 cases in AD group，32 cases in no-progression group and 51 cases in OND group.The level of CSF OPN in AD group was significantly higher than that in no-progression group and OND group （P<0.05）．There was no significant difference in the levels of IL-1β，IL-6，IL-17A，TGF-β1 and IL-4 among three groups after 1 year of follow-up （P>0.05）；the levels of serum OPN and TNF-α in three groups at 1 year of follow-up were statistically significant （P<0.05）；the levels of OPN and TNF-α in AD group were higher than those in no-progression group and OND group （P<0.05）．The result of correlation analysis showed that the levels of OPN in cerebrospinal fluid and in serum were positively correlated with MMSE score at admission （r=0.348，P<0.001；r=0.631，P<0.001），and the level of TNF-α in serum was negatively correlated with MMSE score （r=-0.435，P<0.001）．There were significant differences in MMSE score，CSF OPN and serum OPN in AD group at admission，at diagnosis of AD and after one-year follow-up （P<0.001），as MMSE score was lower at the time of diagnosis of AD and follow-up for one year，and the levels of OPN in cerebrospinal fluid and serum were higher after admission （P<0.05）．Conclusion　CSF OPN level is a potential biomarker for the early identification of MCI which may progress to AD.Serum and CSF OPN and TNF-α were associated with the severity of dementia in AD.

Key words: Alzheimer disease, Mild cognitive impairment, Osteopontin, Inflammation mediators, Correlation analysis

摘要： 目的　评估骨桥蛋白（OPN）以及炎性因子在轻度认知障碍（MCI）患者进展为阿尔茨海默病（AD）中的预测价值。方法　前瞻性分析2015年6月—2017年6月新疆维吾尔自治区中医医院脑病一科收治的MCI患者以及年龄、性别相匹配的非炎症性神经病变（OND）患者，各60例。收集患者临床资料并对其进行病情评估，采用酶联免疫吸附试验（ELISA）检测患者脑脊液和血清OPN水平、血清白介素（IL）-1β、IL-6、IL-17A、转化生长因子（TGF）-β1、肿瘤坏死因子（TNF）-α和IL-4水平。对患者通过门诊和住院随访1年，根据患者在随访结束时的诊断分为AD组、未进展组和OND组。再次检测随访结束时AD组患者血清OPN以及炎性因子水平。结果　随访结束时AD组23例，未进展组32例，OND组51例。入院时3组脑脊液OPN水平比较，差异有统计学意义（P<0.05）；其中AD组脑脊液OPN水平高于未进展组和OND组（P<0.05）。随访1年时，3组IL-1β、IL-6、IL-17A、TGF-β1、IL-4水平比较，差异均无统计学意义（P>0.05）；随访1年时3组血清OPN、TNF-α水平比较，差异均有统计学意义（P<0.05）；其中AD组血清OPN、TNF-α水平均高于未进展组和OND组（P<0.05）。相关性分析结果显示，所有患者入院时脑脊液OPN、血清OPN水平与MMSE评分呈正相关（r=0.348，P<0.001；r=0.631，P<0.001），血清TNF-α水平与MMSE评分呈负相关（r=-0.435，P<0.001）。AD组患者入院时、诊断AD时、随访1年时MMSE评分、脑脊液OPN、血清OPN水平比较，差异均有统计学意义（P<0.001）；其中诊断AD时、随访1年时MMSE评分低于入院时，脑脊液OPN、血清OPN水平高于入院时（P<0.05）。结论　脑脊液OPN水平是早期识别进展为AD的MCI患者的潜在生物标志物，并且血清及脑脊液OPN水平以及TNF-α与AD的痴呆严重程度具有相关性。

关键词: 阿尔茨海默病, 轻度认知障碍, 骨桥蛋白质, 炎症介导素类, 相关性分析