用于区分特发性正常压力脑积水与皮质下缺血性血管病的脑脊液生物标志物

Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease.

作者信息

Manniche Christina, Simonsen Anja Hviid, Hasselbalch Steen Gregers, Andreasson Ulf, Zetterberg Henrik, Blennow Kaj, Høgh Peter, Juhler Marianne, Hejl Anne-Mette

机构信息

Department of Neurology, Danish Dementia Research Centre, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

J Alzheimers Dis. 2020;75(3):937-947. doi: 10.3233/JAD-200036.

DOI:10.3233/JAD-200036

PMID:32390628

Abstract

BACKGROUND

Idiopathic normal pressure hydrocephalus (iNPH) remains a challenge to differentiate from subcortical ischemic vascular disease (SIVD). Despite major research efforts, the cerebrospinal fluid (CSF) biomarker profiles of the two diseases are still not known in detail.

OBJECTIVE

To determine if novel CSF biomarkers, neurofilament light (NFL) reflecting axonal damage, the synaptic protein neurogranin (NG), and the astroglial marker chitinase-3-like protein 1 (YKL-40), and the core Alzheimer's disease (AD) biomarkers, amyloid-β 42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), can differentiate iNPH from SIVD. Patients with AD and healthy controls (HC) were included for comparison purposes.

METHODS

Patients with iNPH (n = 28), SIVD (n = 30), AD (n = 57), and HC (n = 33) were retrospectively included from the Danish Dementia Biobank. All patients with iNPH had effect of shunt surgery with a follow-up period of 4 to 69 months. CSF biomarkers were measured using immunoassays.

RESULTS

Lower levels of NFL, NG, Aβ42, and t-tau were found in patients with iNPH versus SIVD, while YKL-40 and p-tau were similar in the two diseases. NFL and Aβ42 were the most reliable biomarkers to differentiate iNPH from SIVD with an area under the curve (AUC) on 0.82 and 0.80, respectively. Combining NFL with Aβ42, t-tau, and p-tau resulted in an AUC of 0.90, which was equivalent to the diagnostic accuracy of all six biomarkers combined.

CONCLUSION

An addition of NFL to the CSF panel of Aβ42, t-tau, and p-tau may improve the differentiation of iNPH from SIVD.

摘要

背景

特发性正常压力脑积水（iNPH）与皮质下缺血性血管病（SIVD）的鉴别仍然是一项挑战。尽管进行了大量研究，但这两种疾病的脑脊液（CSF）生物标志物谱仍不清楚。

目的

确定反映轴突损伤的新型脑脊液生物标志物神经丝轻链（NFL）、突触蛋白神经颗粒素（NG）、星形胶质细胞标志物几丁质酶-3样蛋白1（YKL-40）以及阿尔茨海默病（AD）核心生物标志物淀粉样β蛋白42（Aβ42）、总tau蛋白（t-tau）、磷酸化tau蛋白（p-tau）能否区分iNPH和SIVD。纳入AD患者和健康对照（HC）用于比较。

方法

从丹麦痴呆生物样本库中回顾性纳入iNPH患者（n = 28）、SIVD患者（n = 30）、AD患者（n = 57）和HC（n = 33）。所有iNPH患者均接受了分流手术，随访期为4至69个月。使用免疫分析法检测脑脊液生物标志物。

结果

与SIVD患者相比，iNPH患者的NFL、NG、Aβ42和t-tau水平较低，而两种疾病中的YKL-40和p-tau相似。NFL和Aβ42是区分iNPH和SIVD最可靠的生物标志物，曲线下面积（AUC）分别为0.82和0.80。将NFL与Aβ42、t-tau和p-tau联合使用，AUC为0.90，这与所有六种生物标志物联合使用时的诊断准确性相当。