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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.

Original publication

DOI

10.3109/21678421.2014.905606

Type

Journal article

Journal

Amyotroph Lateral Scler Frontotemporal Degener

Publication Date

09/2014

Volume

15

Pages

351 - 356

Keywords

TDP-43, amyotrophic lateral sclerosis, biomarker, cerebrospinal fluid, exosomes, frontotemporal lobar degeneration, Aged, DNA-Binding Proteins, Exosomes, Female, Humans, Lymphocytes, Male, Mass Spectrometry, Membrane Proteins, Microscopy, Electron, Transmission, Middle Aged, Molecular Weight, Neurodegenerative Diseases