Department of Neurology, Ulm University, Ulm, Germany; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy.
Department of Neurology, Ulm University, Ulm, Germany.
Neurobiol Aging. 2018 Jul;67:21-22. doi: 10.1016/j.neurobiolaging.2018.02.017. Epub 2018 Feb 27.
Chromogranin A (CgA) is a protein found in large dense-core vesicles of neuroendocrine cells and neurons and regulating secretion. A relevance to amyotrophic lateral sclerosis (ALS) was suggested as its overexpression accelerates disease onset in model systems and it interacts with mutant forms of SOD1. Recently, increased cerebrospinal fluid (CSF) CgA levels have been reported in ALS patients relative to controls. With the aim of confirming this finding, we measured CgA and phosphorylated neurofilament heavy chain (pNFH), an established ALS biomarker, in the CSF of 32 ALS patients and 32 disease controls. ALS patients had clearly increased pNFH levels (p < 0.0001), while CgA levels were only modestly lower relative to controls (p = 0.0265), with wide value overlap and consequently poor discriminative performance. CgA did not correlate with any disease parameters among ALS patients. Our findings suggest that CgA is not a promising clinical biomarker for ALS.
嗜铬粒蛋白 A（CgA）是一种存在于神经内分泌细胞和神经元大致密核心囊泡中的蛋白质，可调节分泌。其过表达会加速模型系统中的疾病发作，并且与 SOD1 的突变形式相互作用，因此与肌萎缩侧索硬化症（ALS）有关。最近，有报道称 ALS 患者的脑脊液（CSF）中 CgA 水平升高相对于对照组。为了证实这一发现，我们测量了 32 名 ALS 患者和 32 名疾病对照组患者 CSF 中的 CgA 和磷酸化神经丝重链（pNFH），这是一种已确立的 ALS 生物标志物。ALS 患者的 pNFH 水平明显升高（p < 0.0001），而 CgA 水平相对于对照组仅略有降低（p = 0.0265），具有广泛的价值重叠，因此具有较差的判别性能。CgA 与 ALS 患者的任何疾病参数均无相关性。我们的研究结果表明，CgA 不是 ALS 的有前途的临床生物标志物。
