TY - JOUR
T1 - TDP-43 plasma levels are higher in amyotrophic lateral sclerosis
AU - Verstraete, Esther
AU - Kuiperij, H. Bea
AU - Van Blitterswijk, Marka M.
AU - Veldink, Jan H.
AU - Schelhaas, H. Jurgen
AU - Van Den Berg, Leonard H.
AU - Verbeek, Marcel M.
N1 - Funding Information:
Wethank 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.
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - Biomarker
KW - ELISA
KW - Plasma
KW - TAR DNA binding protein of 43 kDa (TDP-43)
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U2 - 10.3109/17482968.2012.703208
DO - 10.3109/17482968.2012.703208
M3 - Article
C2 - 22873561
AN - SCOPUS:84865337487
SN - 1748-2968
VL - 13
SP - 446
EP - 451
JO - Amyotrophic Lateral Sclerosis
JF - Amyotrophic Lateral Sclerosis
IS - 5
ER -