Elevated CSF TDP-43 levels in amyotrophic lateral sclerosis: Specificity, sensitivity, and a possible prognostic value

Yu Ichi Noto, Kazumoto Shibuya, Yasunori Sato, Kazuaki Kanai, Sonoko Misawa, Setsu Sawai, Masahiro Mori, Tomoyuki Uchiyama, Sagiri Isose, Saiko Nasu, Yukari Sekiguchi, Yumi Fujimaki, Takashi Kasai, Takahiko Tokuda, Masanori Nakagawa, Satoshi Kuwabara

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Abstract

TAR DNA binding protein of 43 kDa (TDP-43) is likely to be the major pathogenetic protein in amyotrophic lateral sclerosis (ALS). A previous study has shown that levels of TDP-43 in CSF measured by an ELISA are significantly higher for ALS patients than for controls. The aim of this study was to investigate whether elevated CSF TDP-43 levels are specific to ALS, and are associated with clinical profiles in ALS patients. We measured CSF TDP-43 levels by the same ELISA in 27 ALS patients and 50 neurodegenerative or inflammatory disease controls such as Parkinson's disease, multiple sclerosis, and Guillain-Barré syndrome. Results showed that the CSF TDP-43 levels were increased only in ALS patients. Receiver operating characteristic (ROC) analyses showed a sensitivity of 59.3% and a specificity of 96.0%. We also found that lower CSF TDP-43 levels may be associated with shorter survival time. In conclusion, the CSF TDP-43 is a potential biomarker that supports a diagnosis of ALS. Moreover, among ALS patients, lower levels of CSF TDP-43 may reflect the accumulation of TDP-43 in the cortical and spinal motor neurons and thereby shorter survival time, although this should be confirmed in larger prospective studies.

Original languageEnglish
Pages (from-to)140-143
Number of pages4
JournalAmyotrophic Lateral Sclerosis
Volume12
Issue number2
DOIs
Publication statusPublished - 2011 Mar 1

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Keywords

  • Amyotrophic lateral sclerosis
  • ELISA
  • TAR DNA binding protein of 43 kDa (TDP-43)
  • cerebrospinal fluid (CSF)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Noto, Y. I., Shibuya, K., Sato, Y., Kanai, K., Misawa, S., Sawai, S., Mori, M., Uchiyama, T., Isose, S., Nasu, S., Sekiguchi, Y., Fujimaki, Y., Kasai, T., Tokuda, T., Nakagawa, M., & Kuwabara, S. (2011). Elevated CSF TDP-43 levels in amyotrophic lateral sclerosis: Specificity, sensitivity, and a possible prognostic value. Amyotrophic Lateral Sclerosis, 12(2), 140-143. https://doi.org/10.3109/17482968.2010.541263