Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases. Issue 5 (September 2014)

• Record Type: Journal Article
• Authors: Feneberg, Emily; Steinacker, Petra; Lehnert, Stefan; Schneider, Anja; Walther, Paul; Thal, Dietmar R.; Linsenmeier, Miriam; Ludolph, Albert C.; Otto, Markus
• Is Part Of: Amyotrophic lateral sclerosis and frontotemporal degeneration. Volume 15:Issue 5/6(2014)
• Page Start: 351
• Page End: 356
• Publication Date: 2014-09
• Subjects: 616.839
• DOI: 10.3109/21678421.2014.905606
• Languages: English
• ISSNs: 2167-8421

Abstract

<abstract> <title>Abstract</title> <p>TAR DNA-binding protein 43 (TDP-43) is one of the neuropathological hallmarks in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). It is present in patients' blood and cerebrospinal fluid (CSF); however, the source and clinical relevance of TDP-43 measurements in body fluids is uncertain. We investigated paired CSF and serum samples, blood lymphocytes, brain urea fractions and purified exosomes from CSF for TDP-43 by one- (1D), and two-dimensional (2D) Western immunoblotting (WB) and quantitative mass spectrometry (MRM) in patients with ALS, FTLD and non-neurodegenerative diseases. By means of 2D-WB we were able to demonstrate a similar isoform pattern of TDP-43 in lymphocytes, serum and CSF in contrast to that of brain urea fractions with TDP-43 pathology. We found that the TDP-43 CSF to blood concentration ratio is about 1:200. As a possible brain specific fraction we found TDP-43 in exosome preparations from CSF by immunoblot and MRM. We conclude that TDP-43 in CSF originates mainly from blood. Measurements of TDP-43 in CSF and blood are of minor importance as a diagnostic tool, but may be important for monitoring therapy effects of TDP-43 modifying drugs.</p> </abstract>