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一项关于阿尔茨海默病和血管性痴呆患者脑脊液(CSF)tau蛋白的纵向初步研究。

A Pilot Longitudinal Study on Cerebrospinal Fluid (CSF) Tau Protein in Alzheimer's Disease and Vascular Dementia.

作者信息

Wang Haihong, Wang Tao, Qian Shixing, Ba Li, Lin Zhiguang, Xiao Shifu

机构信息

Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Shanghai Arch Psychiatry. 2016 Oct 25;28(5):271-279. doi: 10.11919/j.issn.1002-0829.216068.

Abstract

BACKGROUND

Alzheimer's disease (AD) has high a prevalence rate, high medical costs, and care difficulties, and has become a serious social and economic problem in our aging society. So far, there has not been a reliable and objective diagnostic criteria for AD found. In recent years, there have been many domestic and foreign studies on the biological markers of cerebrospinal fluid in the patients with AD, and high levels of the T-tau, P-tau found in cerebrospinal fluid (CSF) is at this point an indisputable fact. However, the relationship between these markers and the severity of dementia, as well as the development of the disease, should be further studied.

OBJECTIVE

Compare the CSF level of total tau (T-tau) and phosphorylated tau at threonine 231 (P-tau) between patients with moderate to severe Alzheimer's disease (AD) and those with vascular dementia (VD) at baseline, and 6 month follow-up. Observe the differences between patients with AD and control group, as well as the changes as the disease develops.

METHODS

There were 11 patients with moderate AD (10 ≤ MMSE ≤ 20), 10 patients with severe AD (MMSE ≤ 9), and 7 age-matched patients with severe VD at baseline, among which 7 AD patients and 6 VD patients completed the 6 months follow-up. CSF levels of T-tau, P-tau231 were measured with sandwich ELISA.

RESULT

At baseline, the concentrations of the CSF level of T-tau were 470.08 (263.58) pg/mL in the AD group and 208.76 (42.24) pg/mL in the VD group. This difference was statistically significant (Z= -3.369, <0.001). The concentrations of CSF level of P-tau were 90.94 (49.86) pg/mL in the AD group and 42.96 (13.10) pg/mL in the VD group. This difference was also statistically significant (Z = -3.237, <0.001). Compared to patients with severe VD, the concentration of CSF T-tau in patients with severe AD was significantly higher (Z= -2.830, = 0.005), as well as the concentration of CSF P-tau (Z = -2.392, = 0.017). The concentration of CSF P-tau in the patients with moderate AD was significantly higher than that in the patients with severe VD (Z = -2.605, = 0.009). At the 6 months follow-up, there were no statistically significant differences in the changes of CSF T-tau and CSF P-tau concentrations between the AD group and VD group.

CONCLUSION

The CSF level of T-tau and P-tau in the AD patients was significantly higher than that in the VD patients. The concentration of CSF P-tau in the moderate AD patients was significantly higher than that in the patients with severe AD. During the 6 months follow-up, the changes of the CSF concentrations of T-tau and P-tau between AD group and VD group were not statistically significant.

摘要

背景

阿尔茨海默病(AD)患病率高、医疗费用高且护理困难,已成为老龄化社会中严重的社会经济问题。迄今为止,尚未发现可靠且客观的AD诊断标准。近年来,国内外对AD患者脑脊液生物标志物进行了诸多研究,脑脊液(CSF)中T-tau、P-tau水平升高已是不争的事实。然而,这些标志物与痴呆严重程度以及疾病发展之间的关系仍有待进一步研究。

目的

比较中度至重度阿尔茨海默病(AD)患者与血管性痴呆(VD)患者在基线及随访6个月时脑脊液中总tau(T-tau)和苏氨酸231位点磷酸化tau(P-tau)水平。观察AD患者与对照组之间的差异以及疾病发展过程中的变化。

方法

基线时,有11例中度AD患者(10≤MMSE≤20)、10例重度AD患者(MMSE≤9)以及7例年龄匹配的重度VD患者,其中7例AD患者和6例VD患者完成了6个月随访。采用夹心ELISA法检测脑脊液中T-tau、P-tau231水平。

结果

基线时,AD组脑脊液T-tau水平浓度为470.08(263.58)pg/mL,VD组为208.76(42.24)pg/mL。差异具有统计学意义(Z = -3.369,P<0.001)。AD组脑脊液P-tau水平浓度为90.94(49.86)pg/mL,VD组为42.96(13.10)pg/mL。差异同样具有统计学意义(Z = -3.237,P<0.001)。与重度VD患者相比,重度AD患者脑脊液T-tau浓度显著更高(Z = -2.830,P = 0.005),脑脊液P-tau浓度也更高(Z = -2.392,P = 0.017)。中度AD患者脑脊液P-tau浓度显著高于重度VD患者(Z = -2.605,P = 0.009)。随访6个月时,AD组和VD组脑脊液T-tau和脑脊液P-tau浓度变化无统计学意义。

结论

AD患者脑脊液中T-tau和P-tau水平显著高于VD患者。中度AD患者脑脊液P-tau浓度显著高于重度AD患者。随访6个月期间,AD组和VD组脑脊液中T-tau和P-tau浓度变化无统计学意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e2d/5434283/2d5045e33b44/sap-28-271-g001.jpg

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