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Research Article

TDP-43 plasma levels are higher in amyotrophic lateral sclerosis

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Pages 446-451 | Received 07 Mar 2012, Accepted 11 Jun 2012, Published online: 08 Aug 2012
 

Abstract

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.

Acknowledgements

We thank Alexandra Versleijen for technical assistance. This research was supported by The Alzheimer's Drug Discovery Foundation, the Association for Frontotemporal Dementias and The Netherlands ALS Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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