期刊
INTERNATIONAL JOURNAL OF NEUROSCIENCE
卷 124, 期 5, 页码 344-349出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/00207454.2013.848440
关键词
TDP-43; cerebrospinal fluid (CSF); amyotrophic lateral sclerosis (ALS); ELISA; culture supernatant; Guillain-Barre syndrome (GBS)
资金
- Japan Society for the Promotion of Science [22791157]
- Mitsui Life Social Welfare Foundation
- Ministry of Health, Labor and Welfare
- Grants-in-Aid for Scientific Research [25110738, 23700433, 23240050, 24500429, 22791157] Funding Source: KAKEN
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-Barre 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.
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