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

Autor(es): Hosokawa Masato,Arai Tetsuaki,Yamashita Makiko,Tsuji Hiroshi,Nonaka Takashi,Masuda-Suzukake Masami,Tamaoka Akira,Hasegawa Masato,Akiyama Haruhiko

Resumo: 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.

Palavras-Chave: TDP-43; Cerebrospinal fluid (CSF); Amyotrophic lateral sclerosis (ALS); ELISA; Culture supernatant; Guillain-Barré syndrome (GBS)

Imprenta: The International Journal of Neuroscience, v. 124, n. 5, p. 344-349, 2014

Identificador do objeto digital: 10.3109/00207454.2013.848440

Descritores: Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - DNA ; Guillain-Barre Syndrome - Proteins

Data de publicação: 2014