De Vos Ann, Bjerke Maria, Brouns Raf, De Roeck Naomi, Jacobs Dirk, Van den Abbeele Lien, Guldolf Kaat, Zetterberg Henrik, Blennow Kaj, Engelborghs Sebastiaan, Vanmechelen Eugeen
ADx NeuroSciences NV, Technologiepark 4, 9052, Ghent, Belgium.
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
BMC Neurol. 2017 Aug 30;17(1):170. doi: 10.1186/s12883-017-0945-8.
While neurogranin has no value as plasma biomarker for Alzheimer's disease, it may be a potential blood biomarker for traumatic brain injury. This evokes the question whether there are changes in neurogranin levels in blood in other conditions of brain injury, such as acute ischemic stroke (AIS).
We therefore explored neurogranin in paired cerebrospinal fluid (CSF)/plasma samples of AIS patients (n = 50) from a well-described prospective study. In parallel, we investigated another neuronal protein, i.e. tau, which has already been suggested as potential AIS biomarker in CSF and blood. ELISA as well as Single Molecule Array (Simoa) technology were used for the biochemical analyses. Statistical analyses included Shapiro-Wilk testing, Mann-Whitney analyses and Pearson's correlation analysis.
In contrast to tau, of which high levels in both CSF and plasma were related to stroke characteristics like severity and long-term outcome, plasma neurogranin levels were only correlated with infarct volume. Likewise, CSF neurogranin levels were significantly higher in patients with an infarct volume > 5 mL than in patients with smaller infarct volumes. Finally, neurogranin and tau were significantly correlated in CSF, whereas a weaker relationship was observed in plasma.
These findings indicate that although plasma and CSF neurogranin may reflect the volume of acute cerebral ischemia, this synaptic protein is less likely to be a potential AIS biomarker. Levels of tau correlated with severity and outcome of stroke in both plasma and CSF, in the present study as well as previous reports, confirming the potential of tau as an AIS biomarker.
虽然神经颗粒蛋白作为阿尔茨海默病的血浆生物标志物没有价值,但它可能是创伤性脑损伤的潜在血液生物标志物。这就引发了一个问题,即在其他脑损伤情况下,如急性缺血性中风(AIS),血液中神经颗粒蛋白水平是否会发生变化。
因此,我们在一项详细描述的前瞻性研究中,对AIS患者(n = 50)的配对脑脊液(CSF)/血浆样本中的神经颗粒蛋白进行了探索。同时,我们研究了另一种神经元蛋白,即tau蛋白,它已被认为是CSF和血液中潜在的AIS生物标志物。采用酶联免疫吸附测定(ELISA)以及单分子阵列(Simoa)技术进行生化分析。统计分析包括夏皮罗-威尔克检验、曼-惠特尼分析和皮尔逊相关分析。
与tau蛋白不同,CSF和血浆中tau蛋白的高水平与中风特征如严重程度和长期预后相关,而血浆神经颗粒蛋白水平仅与梗死体积相关。同样,梗死体积>5 mL的患者CSF神经颗粒蛋白水平显著高于梗死体积较小的患者。最后,神经颗粒蛋白和tau蛋白在CSF中显著相关,而在血浆中观察到的相关性较弱。
这些发现表明,虽然血浆和CSF神经颗粒蛋白可能反映急性脑缺血的体积,但这种突触蛋白不太可能是潜在的AIS生物标志物。在本研究以及先前的报告中,tau蛋白水平与血浆和CSF中中风的严重程度和预后相关,证实了tau蛋白作为AIS生物标志物的潜力。