Department of Neurology, Aviation General Hospital of China Medical University & Beijing Institute of Translational Medicine, Chinese Academy of Sciences, No. 3 Anwai Beiyuan Road, Chaoyang District, Beijing, 100012, China.
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, Cornell Memory Disorders Program, 428 East 72 Street, Suite 500, New York, NY, 10021, USA.
Fluids Barriers CNS. 2017 May 10;14(1):13. doi: 10.1186/s12987-017-0062-5.
The purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) as potential diagnostic biomarkers for idiopathic normal-pressure hydrocephalus (iNPH) and to assess their utility indistinguishing patients with iNPH from those with Alzheimer disease (AD) and healthy normal controls.
Studies were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Database, VIP Chinese database, and Chinese Bio-medicine Database (CBM) before August 2016. The standardized mean difference (SMD) and 95% confidence interval (CI), comparing CSF Aβ42, t-tau, and p-tau levels between iNPH, AD and healthy controls, were calculated using random-effects models. Subgroup analyses were created according to ethnicity (Caucasian or Asian) and CSF type (lumbar or ventricular), and the publication bias was estimated using Egger's test and the Begg's test.
A total of 10 studies including 413 patients with iNPH, 186 patients with AD and 147 healthy controls were included in this systematic review and meta-analysis. The concentrations of CSF t-tau, and p-tau were significantly lower in iNPH patients compared to AD (SMD = -1.26, 95% CI -1.95 to -0.57, P = 0.0004; SMD = -1.54, 95% CI -2.34 to -0.74, P = 0.0002, respectively) and lower than healthy controls (SMD = -0.80, 95% CI -1.50 to -0.09, P = 0.03; SMD = -1.12, 95% CI -1.38 to -0.86, P < 0.00001, respectively). Patients with iNPH had significantly lower Aβ42 levels compared with controls (SMD = -1.14, 95% CI -1.74 to -0.55, P = 0.0002), and slightly higher Aβ42 levels compared with AD patients (SMD = 0.32, 95% CI 0.00-0.63, P = 0.05). Subgroup analyses showed that the outcomes may have been influenced by ethnicity and CSF source. Compared to AD, overall sensitivity in differentiating iNPH was 0.813 (95% CI 0.636-0.928) for Aβ42, 0.828 (95% CI 0.732-0.900) for t-tau, 0.943 (95% CI 0.871-0.981) for p-tau. Relative to AD, overall specificity in differentiating iNPH was 0.506 (95% CI 0.393-0.619) for Aβ42, 0.842 (95% CI 0.756-0.907) for t-tau, 0.851 (95% CI 0.767-0.914) for p-tau.
The results of our meta-analysis suggest that iNPH may be associated with significantly reduced levels of CSF Aβ42, t-tau and p-tau compared to the healthy normal state. Compared to AD, both t-tau and p-tau were significantly decreased in iNPH, but CSF Aβ42 was slightly increased. Prospective studies are needed to further assess the clinical utility of these and other CSF biomarkers in assisting in the diagnosis of iNPH and differentiating it from AD and other neurodegenerative disorders.
本系统评价和荟萃分析的目的是评估脑脊液（CSF）β淀粉样蛋白 42（Aβ42）、总tau（t-tau）和磷酸化tau（p-tau）作为特发性正常压力脑积水（iNPH）潜在诊断生物标志物的性能，并评估它们在鉴别 iNPH 患者与阿尔茨海默病（AD）和健康正常对照者中的效用。
通过检索 PubMed、Embase、Cochrane 图书馆、Web of Science、中国国家知识基础设施（CNKI）、万方中国期刊数据库、维普中文科技期刊数据库和中国生物医学文献数据库（CBM），于 2016 年 8 月前检索到相关研究。使用随机效应模型计算 CSF Aβ42、t-tau 和 p-tau 水平在 iNPH、AD 和健康对照组之间的标准化均数差（SMD）和 95%置信区间（CI）。根据种族（白种人或亚洲人）和 CSF 类型（腰椎或脑室）进行亚组分析，并使用 Egger 检验和 Begg 检验估计发表偏倚。
本系统评价和荟萃分析共纳入 10 项研究，包括 413 例 iNPH 患者、186 例 AD 患者和 147 例健康对照者。与 AD 患者相比，iNPH 患者的 CSF t-tau 和 p-tau 浓度明显降低（SMD=-1.26，95%CI-1.95 至-0.57，P=0.0004；SMD=-1.54，95%CI-2.34 至-0.74，P=0.0002），且明显低于健康对照组（SMD=-0.80，95%CI-1.50 至-0.09，P=0.03；SMD=-1.12，95%CI-1.38 至-0.86，P<0.00001）。与对照组相比，iNPH 患者的 CSF Aβ42 水平明显降低（SMD=-1.14，95%CI-1.74 至-0.55，P=0.0002），与 AD 患者相比，CSF Aβ42 水平略有升高（SMD=0.32，95%CI 0.00 至 0.63，P=0.05）。亚组分析表明，种族和 CSF 来源可能影响研究结果。与 AD 相比，Aβ42 鉴别 iNPH 的总敏感性为 0.813（95%CI 0.636-0.928），t-tau 为 0.828（95%CI 0.732-0.900），p-tau 为 0.943（95%CI 0.871-0.981）。与 AD 相比，Aβ42 鉴别 iNPH 的总特异性为 0.506（95%CI 0.393-0.619），t-tau 为 0.842（95%CI 0.756-0.907），p-tau 为 0.851（95%CI 0.767-0.914）。
本荟萃分析结果表明，与健康正常状态相比，iNPH 可能与 CSF Aβ42、t-tau 和 p-tau 水平显著降低相关。与 AD 相比，iNPH 患者的 t-tau 和 p-tau 明显降低，但 CSF Aβ42 略有升高。需要进一步进行前瞻性研究，以评估这些和其他 CSF 生物标志物在辅助 iNPH 诊断和鉴别 AD 及其他神经退行性疾病中的临床效用。
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