Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Fundación Valle del Lili, Cali, Icesi University, Valle del Cauca, Colombia.
Amyotroph Lateral Scler Frontotemporal Degener. 2021 Nov;22(7-8):517-527. doi: 10.1080/21678421.2021.1912100. Epub 2021 Apr 30.
C9ORF72 hexanucleotide expansion is the most common genetic cause of familial amyotrophic lateral sclerosis (ALS)/fronto-temporal dementia (FTD) disease spectrum. Even though three major mechanisms of disease pathogenesis have been proposed, we lack detailed understanding of the factors that influence disease onset and progression. We sought to characterize cerebrospinal fluid and sera of C9ORF72 patients via a multiplex assay of 41 chemokines and cytokines in comparison to neurological controls and sporadic ALS patients. We found an increase in synthesis of pro-inflammatory chemokines and cytokines in disease samples and particularly in C9ORF72 patients in comparison to controls. We provide evidence that a CSF pro-inflammatory signature is a feature of C9ORF72-mediated disease.
C9ORF72 六核苷酸扩展是家族性肌萎缩侧索硬化症（ALS）/额颞叶痴呆（FTD）疾病谱中最常见的遗传原因。尽管已经提出了三种主要的发病机制，但我们缺乏对影响疾病发作和进展的因素的详细了解。我们试图通过对 41 种趋化因子和细胞因子进行多重分析，来对 C9ORF72 患者的脑脊液和血清进行特征描述，并与神经学对照组和散发性 ALS 患者进行比较。我们发现，与对照组相比，疾病样本中促炎趋化因子和细胞因子的合成增加，尤其是 C9ORF72 患者。我们提供的证据表明，CSF 促炎特征是 C9ORF72 介导疾病的一个特征。
