Kang Kyunghun, Ko Pan-Woo, Jin Myungwon, Suk Kyoungho, Lee Ho-Won
Department of Neurology, Kyungpook National University School of Medicine, 50 Samdeok-dong 2-ga, Jung-gu, Daegu 700-721, South Korea.
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, South Korea; Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu, South Korea.
J Clin Neurosci. 2014 Aug;21(8):1398-403. doi: 10.1016/j.jocn.2013.11.039. Epub 2014 May 14.
Cerebrospinal fluid (CSF) biomarkers, including soluble amyloid β-42 (Aβ-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer's disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers Aβ-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF Aβ-42 correlated with poor cognitive performance (r=0.687, p<0.001 for Korean Mini Mental State Examination; r=0.568, p=0.001 for Frontal Assessment Battery; r=-0.439, p=0.014 for iNPH grading scale [iNPHGS] cognitive score; r=-0.588, p=0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r=-0.624, p<0.001 for Timed Up and Go Test; r=-0.652, p<0.001 for 10meter walking test; r=-0.578, p=0.001 for Gait Status Scale; r=-0.543, p=0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/Aβ-42 ratios were significantly higher in CSFTT non-responders compared to responders (p=0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses.
脑脊液（CSF）生物标志物，包括可溶性淀粉样β-42（Aβ-42）和磷酸化tau蛋白（P-tau），反映了阿尔茨海默病（AD）的核心病理生理特征。AD在特发性正常压力脑积水（iNPH）老年患者中常为伴随病理情况，且AD和iNPH存在一些相似的脑脊液动力学改变。因此，我们研究了iNPH患者腰椎脑脊液生物标志物Aβ-42和P-tau与临床参数之间的关系，以及脑脊液穿刺试验（CSFTT）反应者和无反应者之间这些生物标志物的差异。最终分析纳入了31例iNPH患者（14例CSFTT反应者和17例CSFTT无反应者）。我们发现脑脊液Aβ-42水平较低与认知功能较差相关（韩国简易精神状态检查表，r = 0.687，p < 0.001；额叶评估量表，r = 0.568，p = 0.001；iNPH分级量表[iNPHGS]认知评分，r = -0.439，p = 0.014；临床痴呆评定量表，r = -0.588，p = 0.001），脑脊液P-tau水平较低与步态功能障碍相关（计时起立行走试验，r = -0.624，p < 0.001；10米步行试验，r = -0.652，p < 0.001；步态状态量表，r = -0.578，p = 0.001；iNPHGS步态评分，r = -0.543，p = 0.002）。在亚组分析中，CSFTT无反应者的脑脊液P-tau/Aβ-42比值显著高于反应者（p = 0.027）。提出了两种推测。其一，脑脊液生物标志物可能在iNPH的不同症状（如认知和步态）方面发挥不同的特征性作用。其二，iNPH患者的合并AD病理可能影响对CSFTT的反应。有必要开展更大规模的研究，联合使用与AD相关的其他生物标志物来评估这些假设。
