Verstraete Esther, Kuiperij H Bea, van Blitterswijk Marka M, Veldink Jan H, Schelhaas H Jurgen, van den Berg Leonard H, Verbeek Marcel M
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
Amyotroph Lateral Scler. 2012 Sep;13(5):446-51. doi: 10.3109/17482968.2012.703208. Epub 2012 Aug 8.
Our objective was to investigate TDP-43 plasma levels in patients with amyotrophic lateral sclerosis (ALS). TDP-43 has been identified as a major component of protein inclusions in the brain of patients with ALS; mutations in the corresponding gene (TARDBP) have also been identified. Although increased TDP-43 levels have been reported in the cerebrospinal fluid, plasma levels have not yet been assessed in patients with ALS. TDP-43 levels were quantified by sandwich ELISA in plasma of 219 patients and 100 controls. In addition, we sequenced exon 6 of TARDBP, and performed longitudinal TDP-43 plasma measurements in a subset of patients. Results showed that TDP-43 plasma levels were significantly increased in patients with ALS (p=0.023) and we found a positive correlation with age in patients and controls. Longitudinal measurements of TDP-43 plasma levels showed an increase in only one patient, with stable levels in five others. Three TARDBP variations were identified in the ALS group (1.7%), but the association with TDP-43 plasma levels was ambiguous. In conclusion, our data indicate that TDP-43 plasma levels may have potential as a marker for ALS. A genotype-phenotype relationship could not, however, be established in this cohort.
我们的目标是研究肌萎缩侧索硬化症（ALS）患者的TDP-43血浆水平。TDP-43已被确定为ALS患者大脑中蛋白质内含物的主要成分；相应基因（TARDBP）的突变也已被发现。尽管脑脊液中TDP-43水平升高已有报道，但ALS患者的血浆水平尚未得到评估。通过夹心ELISA对219例患者和100例对照的血浆中TDP-43水平进行定量。此外，我们对TARDBP的第6外显子进行了测序，并对一部分患者进行了TDP-43血浆水平的纵向测量。结果显示，ALS患者的TDP-43血浆水平显著升高（p=0.023），并且我们发现患者和对照中TDP-43血浆水平与年龄呈正相关。TDP-43血浆水平的纵向测量显示，只有1例患者水平升高，其他5例患者水平稳定。在ALS组中鉴定出3种TARDBP变异（1.7%），但与TDP-43血浆水平的关联不明确。总之，我们的数据表明，TDP-43血浆水平可能具有作为ALS标志物的潜力。然而，在该队列中未能建立基因型-表型关系。
