TDP-43 as structure-based biomarker in amyotrophic lateral sclerosis

Ann Clin Transl Neurol. 2021 Jan;8(1):271-277. doi: 10.1002/acn3.51256. Epub 2020 Dec 2.

Abstract

Pathologic alterations of Transactivation response DNA-binding protein 43 kilo Dalton (TDP-43) are a major hallmark of amyotrophic lateral sclerosis (ALS). In this pilot study, we analyzed the secondary structure distribution of TDP-43 in cerebrospinal fluid of ALS patients (n = 36) compared to Parkinson´s disease patients (PD; n = 30) and further controls (Ctrl; n = 24) using the immuno-infrared sensor technology. ALS patients could be discriminated from PD and Ctrl with a sensitivity/specificity of 89 %/77 % and 89 %/83 %, respectively. Our findings demonstrate that TDP-43 misfolding measured by the immuno-infrared sensor technology has the potential to serve as a biomarker candidate for ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Amyotrophic Lateral Sclerosis / diagnosis*
  • Biomarkers / cerebrospinal fluid*
  • DNA-Binding Proteins / cerebrospinal fluid*
  • DNA-Binding Proteins / chemistry
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Protein Structure, Secondary
  • Sensitivity and Specificity
  • Spectrophotometry, Infrared / methods

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • TARDBP protein, human

Grants and funding

This work was funded by Center for Protein Diagnostics (ProDi) grant ; Hermann und Lilly Schilling‐Stiftung für medizinische Forschung im Stifterverband grant ; Protein Research Unit within Europe (PURE) grant ; niemALS aufgeben e. V. grant .