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

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.

Key words::

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

Acknowledgements

This work was supported by grants-in-aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labor and Welfare of Japan (MN and SK).

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