期刊
JOURNAL OF THE NEUROLOGICAL SCIENCES
卷 418, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jns.2020.117070
关键词
Amyotrophic lateral sclerosis; Plasma; TDP-43; Exosome
资金
- Taipei Medical University [MOHW104-TDU-B-212-113001]
- Shuang-Ho Hospital (Ministry of Health and Welfare) [108TMU-SHH-13]
Objective: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease with characteristic of progressive general muscle weakness and atrophy. ALS is still lack of efficient treatment and laboratory biomarkers. In this study, we longitudinally examined ALS patients' peripheral blood to search potential biomarkers. 18 ALS patients aged between 20 and 65 years were recruited in a clinical trial and longitudinal plasma samples were obtained and analyzed at baseline, 1, 3, 6 and 12 months follow up. Neurofilament light chain (NFL), phosphorylated neurofilament heavy chain (pNFH) by ELISA and exosomal TAR DNA-binding protein-43 (TDP-43) ratio were measured by flow cytometry assay in isolated exosomes Results: Exosomal TDP-43 ratio significantly changed in 3-month (increased 60.8 +/- 18.9%, p = 0.0005) and 6-month (increased 60.2 +/- 32.6%, p = 0.0291) follow-up and close to significance at 12-month follow-up (increased 12.8 +/- 10.8%, p = 0.0524). When subclassifying patients into rapid and slow progression groups, NFL but not pNFH is significantly higher in the rapid progression group at baseline (22.74 +/- 1.66 pg/mL vs. 43.96 +/- 12.87 pg/mL, p = 0.0136) and at 3-month follow-up (28.40 +/- 3.39 pg/mL vs. 40.33 +/- 5.44 pg/mL, p = 0.0356). Conclusion: In this study, we found exosomal TDP-43 ratio was increasing along with follow-up at 3 and 6 months and NFL levels in plasma was associated with rapid progression in ALS patients. In addition to NFL, exosomal TDP-43 ratio might be a potential candidate of biomarkers for ALS long-term follow-up studies.
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