Differential diagnosis of amyotrophic lateral sclerosis from Guillain-Barré syndrome by quantitative determination of TDP-43 in cerebrospinal fluid.

Abstract

The aim of this study was to investigate whether an increased level of TAR DNA-binding protein 43 (TDP-43) in the cerebrospinal fluid (CSF) could be a biomarker for amyotrophic lateral sclerosis (ALS) and facilitate differential diagnosis of ALS from peripheral motor neuropathy. TDP-43 is the major constituent of neuronal and glial inclusions that neuropathologically characterize both ALS and tau-negative frontotemporal lobar degeneration. Recent discoveries of various missense mutations in the TDP-43 gene in familial ALS indicate a pivotal role of the aberrant accumulation of TDP-43 in neurodegeneration. Increased TDP-43 in the CSF could be a hallmark of ALS and other TDP-43 proteinopathy. Sandwich enzyme-linked immunosorbent assay (ELISA) was established to measure the concentration of TDP-43 in biological fluids. Culture supernatants of cells transfected with various TDP-43 constructs were used to confirm that the ELISA detected TDP-43. TDP-43 in the culture supernatant of TDP-43 transfected cells was detected by immunoprecipitation with subsequent immunoblotting and concentrations were successfully measured by sandwich ELISA. We then measured TDP-43 concentrations in the CSF of patients with ALS and Guillain-Barré syndrome (GBS). TDP-43 concentrations in CSF were significantly higher in ALS than in GBS (p = 0.016). The sensitivity of the diagnostic test was 71.4% and the specificity was 84.6%. Quantitative determination of TDP-43 concentrations in the CSF by sandwich ELISA is a potential laboratory test for differentiating ALS from peripheral motor neuropathies such as GBS.

• Authors: Masato Hosokawa, Tetsuaki Arai, Makiko Yamashita, Hiroshi Tsuji, Takashi Nonaka, Masami Masuda-Suzukake, Akira Tamaoka, Masato Hasegawa, Haruhiko Akiyama
• Journal: The International journal of neuroscience (Int J Neurosci) Vol. 124 Issue 5 Pg. 344-9 (May 2014) ISSN: 1563-5279 [Electronic] England
• PMID: 24066851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• DNA-Binding Proteins

Topics

• Adult
• Aged
• Amyotrophic Lateral Sclerosis (cerebrospinal fluid, diagnosis)
• Biomarkers (cerebrospinal fluid)
• Cell Line, Tumor
• DNA-Binding Proteins (cerebrospinal fluid)
• Diagnosis, Differential
• Enzyme-Linked Immunosorbent Assay
• Female
• Guillain-Barre Syndrome (cerebrospinal fluid, diagnosis)
• Humans
• Immunoprecipitation (methods)
• Male
• Middle Aged
• TDP-43 Proteinopathies (cerebrospinal fluid)
• Young Adult