Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases

Autor: Albert C. Ludolph, Petra Steinacker, Dietmar Rudolf Thal, Miriam Linsenmeier, Stefan Lehnert, Anja Schneider, Paul Walther, Markus Otto, Emily Feneberg
Rok vydání: 2014
Předmět:
Male
Gene isoform
Pathology
medicine.medical_specialty
diagnosis [Neurodegenerative Diseases]
Exosomes
Exosome
Mass Spectrometry
blood [DNA-Binding Proteins]
Cerebrospinal fluid
Microscopy
Electron
Transmission
metabolism [Exosomes]
mental disorders
Humans
Medicine
Clinical significance
Lymphocytes
ddc:610
Amyotrophic lateral sclerosis
Aged
ultrastructure [Exosomes]
business.industry
ultrastructure [DNA-Binding Proteins]
Membrane Proteins
nutritional and metabolic diseases
Neurodegenerative Diseases
Frontotemporal lobar degeneration
Middle Aged
medicine.disease
Microvesicles
nervous system diseases
Molecular Weight
DNA-Binding Proteins
Neurology
blood [Neurodegenerative Diseases]
metabolism [Lymphocytes]
cerebrospinal fluid [Neurodegenerative Diseases]
Biomarker (medicine)
cerebrospinal fluid [DNA-Binding Proteins]
Female
Neurology (clinical)
business
flotillins
metabolism [Membrane Proteins]
Zdroj: Amyotrophic lateral sclerosis & frontotemporal degeneration 15(5-6), 351-356 (2014). doi:10.3109/21678421.2014.905606
ISSN: 2167-9223
2167-8421
DOI: 10.3109/21678421.2014.905606
Popis: 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.
Databáze: OpenAIRE
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