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Arch Neurol. 2008 Nov;65(11):1481-7. doi: 10.1001/archneur.65.11.1481.

TDP-43 in cerebrospinal fluid of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Author information

1
Department of Neurology, University of Ulm, Ulm, Germany.

Abstract

BACKGROUND:

Recently, TAR DNA-binding protein 43 (TDP-43) was identified as the major component of ubiquitin-positive tau-negative neuronal and glial inclusions in the most common form of frontotemporal lobar degeneration (FTLD) and in amyotrophic lateral sclerosis (ALS). It was demonstrated that different TDP-43 profiles correspond to clinical phenotypes of FTLD or ALS subgroups, and the differential diagnostic potential of TDP-43 was suggested.

OBJECTIVES:

To examine TDP-43 in cerebrospinal fluid (CSF) and to analyze whether it could serve as a diagnostic marker.

DESIGN:

We characterized CSF TDP-43 by immunoblot using different TDP-43 antibodies and determined the relative TDP-43 levels in CSF samples from patients.

SETTING:

Academic research.

PATIENTS:

Twelve patients with FTLD, 15 patients with ALS, 9 patients with ALS plus FTLD, 3 patients with ALS plus additional signs of frontal disinhibition, and 13 control subjects.

MAIN OUTCOME MEASURES:

Results of TDP-43 immunoblot.

RESULTS:

Polyclonal TDP-43 antibodies recognized a 45-kDa band in all analyzed samples. Two monoclonal and N-terminus-specific antibodies did not detect any specific bands, but C-terminus-specific antibodies detected a 45-kDa band and additional bands at approximately 20 kDa in all CSF samples. Relative quantification of 45-kDa bands revealed significant differences among the diagnostic groups (P =.046). Specifically, patients with ALS (P =.03) and FTLD (P =.02) had higher TDP-43 levels than controls but with a prominent overlap of values.

CONCLUSION:

Although there is no evidence of pathologically altered TDP-43 proteins in CSF, TDP-43 levels in CSF might aid in characterizing subgroups of patients across the ALS and FTLD disease spectrum.

PMID:
19001167
PMCID:
PMC2690860
DOI:
10.1001/archneur.65.11.1481
[Indexed for MEDLINE]
Free PMC Article

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