Mao Chenhui, Sha Longze, Liu Caiyan, Chu Shanshan, Li Jie, Huang Xinying, Lei Dan, Wang Jie, Dong Liling, Xu Qi, Peng Bin, Cui Li-Ying, Gao Jing
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science/Peking Union Medical College, Beijing, China.
Institute of Basic Medicine, Chinese Academy of Medical Science/Peking Union Medical College, Beijing, China.
Neurodegener Dis. 2020;20(5-6):165-172. doi: 10.1159/000514052. Epub 2021 Jun 2.
Idiopathic normal pressure hydrocephalus (iNPH) is one of the potentially reversible dementias. Early and accurate diagnosis is important for patients' prognosis. Emerging evidence shows fluid biomarkers are useful in diagnosis and pathophysiological research of iNPH.
Probable iNPH and Alzheimer's disease (AD) patients were recruited. Clinical diagnosis was performed according to international guidelines. CSF collection complied with a standard protocol. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aβ42, and NfL.
Twenty-seven iNPH, 27 AD, and 18 controls were included. The profiles of CSF t-tau, p-tau181, and t-tau/Aβ42 in the iNPH and AD were significantly different (p < 0.0001). The profiles of CSF t-tau, p-tau181, and t-tau/Aβ42 in the iNPH and control were not different (p > 0.05). Level of CSF Aβ42 in iNPH was significantly lower than control (p < 0.0001) and also significantly higher than AD (p < 0.05). NfL level in iNPH and AD was increased, but its level in iNPH was significantly lower than that in AD (p = 0.005). NfL and t-tau level in the iNPH group was significantly correlated (coefficient = 0.649, p = 0.005), but not in AD (coefficient = 0.298, p = 0.157).
Alzheimer's CSF biomarker profile of iNPH subjects showed moderately decreased Aβ42 and normal t-tau, p-tau181, and t-tau/Aβ42, which was distinguishable from AD. The different profiles and correlation of t-tau and NfL suggested different pathophysiology of AD and iNPH. t-tau was relatively an AD-specific neurodegenerative biomarker compared to NfL.
特发性正常压力脑积水（iNPH）是潜在可逆转的痴呆症之一。早期准确诊断对患者预后很重要。新出现的证据表明，脑脊液生物标志物在iNPH的诊断和病理生理学研究中很有用。
招募可能患有iNPH和阿尔茨海默病（AD）的患者。根据国际指南进行临床诊断。脑脊液采集遵循标准方案。使用市售的ELISA试剂盒测量脑脊液中的总tau蛋白（t-tau）、磷酸化tau蛋白181（p-tau181）、淀粉样蛋白β42（Aβ42）和神经丝轻链（NfL）。
纳入27例iNPH患者、27例AD患者和18例对照。iNPH组和AD组脑脊液t-tau、p-tau181和t-tau/Aβ42的水平有显著差异（p<0.0001）。iNPH组和对照组脑脊液t-tau、p-tau181和t-tau/Aβ42的水平无差异（p>0.05）。iNPH组脑脊液Aβ42水平显著低于对照组（p<0.0001），但显著高于AD组（p<0.05）。iNPH组和AD组的NfL水平升高，但iNPH组的NfL水平显著低于AD组（p=0.005）。iNPH组NfL与t-tau水平显著相关（系数=0.649，p=0.005），而AD组无相关性（系数=0.298，p=0.157）。
iNPH患者脑脊液阿尔茨海默病生物标志物谱显示Aβ42适度降低，t-tau、p-tau181和t-tau/Aβ42正常，这与AD不同。t-tau和NfL的不同谱及相关性提示AD和iNPH有不同的病理生理学。与NfL相比，t-tau相对是AD特异性的神经退行性生物标志物。
