Differential diagnosis of amyotrophic lateral sclerosis from Guillain-Barré syndrome by quantitative determination of TDP-43 in cerebrospinal fluid.
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.
1Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science , Tokyo , Japan.
Masato
M
Hosokawa
Tetsuaki
T
Arai
Makiko
M
Yamashita
Hiroshi
H
Tsuji
Takashi
T
Nonaka
Masami
M
Masuda-Suzukake
Akira
A
Tamaoka
Masato
M
Hasegawa
Haruhiko
H
Akiyama
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000134:cerebrospinal fluid*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020275:Guillain-Barre Syndrome / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D008875:Middle Aged; D057177:TDP-43 Proteinopathies / Q000134:cerebrospinal fluid*; D055815:Young Adult
D015415:Biomarkers; D004268:DNA-Binding Proteins