Lang Veronika, Zille Marietta, Infante-Duarte Carmen, Jarius Sven, Jahn Holger, Paul Friedemann, Ruprecht Klemens, Pina Ana Luisa
Department of Neurosurgery, Experimental Neurosurgery, Charité - Universitätsmedizin, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin, Berlin, Germany.
Department of Experimental Neurology, Center for Stroke Research Berlin, Charité - Universitätsmedizin, Berlin, Germany; Department of Neurology and Neuroscience, The Burke Medical Research Institute, Weill Medical College of Cornell University, White Plains, NY, USA.
J Neurol Sci. 2017 Apr 15;375:123-128. doi: 10.1016/j.jns.2017.01.051. Epub 2017 Jan 17.
Pigment-epithelium derived factor (PEDF) is a neurotrophic factor with neuroprotective, anti-tumorigenic, and anti-angiogenic effects. Elevated levels of PEDF have previously been proposed as a cerebrospinal fluid (CSF) biomarker for Alzheimer's disease. However, the origin of PEDF in CSF, i.e. whether it is derived from the brain or from the systemic circulation, and the specificity of this finding hitherto remained unclear. Here, we analyzed levels of PEDF in paired CSF and serum samples by ELISA in patients with Alzheimer's disease (AD, n=12), frontotemporal dementia (FTD, n=6), vascular dementia (n=4), bacterial meningitis (n=8), multiple sclerosis (n=32), pseudotumor cerebri (n=36), and diverse non-inflammatory neurological diseases (n=19). We established CSF/serum quotient diagrams to determine the fraction of intrathecally synthesized PEDF in CSF. We found that PEDF is significantly increased in CSF of patients with AD, FTD, and bacterial meningitis. Remarkably, PEDF concentrations were also significantly elevated in serum of patients with AD. CSF/serum quotient diagrams demonstrated that elevated PEDF concentrations in CSF of patients with AD are mostly due to elevated PEDF concentrations in serum. These findings underscore the importance of relating concentrations of proteins in CSF to their respective concentrations in serum to avoid erroneous interpretations of increased protein concentrations in lumbar CSF.
色素上皮衍生因子（PEDF）是一种具有神经保护、抗肿瘤和抗血管生成作用的神经营养因子。此前有人提出，脑脊液（CSF）中PEDF水平升高可作为阿尔茨海默病的生物标志物。然而，CSF中PEDF的来源，即它是源自大脑还是体循环，以及这一发现的特异性至今仍不清楚。在此，我们通过酶联免疫吸附测定（ELISA）分析了阿尔茨海默病患者（AD，n = 12）、额颞叶痴呆患者（FTD，n = 6）、血管性痴呆患者（n = 4）、细菌性脑膜炎患者（n = 8）、多发性硬化症患者（n = 32）、假性脑瘤患者（n = 36）以及各种非炎性神经系统疾病患者（n = 19）配对的CSF和血清样本中PEDF的水平。我们建立了CSF/血清商数图，以确定CSF中鞘内合成的PEDF的比例。我们发现，AD、FTD和细菌性脑膜炎患者的CSF中PEDF显著增加。值得注意的是，AD患者的血清中PEDF浓度也显著升高。CSF/血清商数图表明，AD患者CSF中PEDF浓度升高主要是由于血清中PEDF浓度升高。这些发现强调了将CSF中蛋白质浓度与其血清中各自浓度相关联的重要性，以避免对腰椎CSF中蛋白质浓度升高的错误解读。
