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

TDP-43 作为肌萎缩侧索硬化症的结构生物标志物

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作者:Léon Beyer, René Günther, Jan Christoph Koch, Stephan Klebe, Tim Hagenacker, Paul Lingor, Anne-Sophie Biesalski, Andreas Hermann, Andreas Nabers, Ralf Gold, Lars Tönges, Klaus Gerwert

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.

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