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

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.

• Authors: Petra Steinacker, Corinna Hendrich, Anne D Sperfeld, Sarah Jesse, Christine A F von Arnim, Stefan Lehnert, Alice Pabst, Ingo Uttner, Hayrettin Tumani, Virginia M-Y Lee, John Q Trojanowski, Hans A Kretzschmar, Albert Ludolph, Manuela Neumann, Markus Otto
• Journal: Archives of neurology (Arch Neurol) Vol. 65 Issue 11 Pg. 1481-7 (Nov 2008) ISSN: 1538-3687 [Electronic] United States
• PMID: 19001167 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• DNA-Binding Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Amyotrophic Lateral Sclerosis (cerebrospinal fluid, complications, diagnosis, psychology)
• Biomarkers (cerebrospinal fluid)
• DNA-Binding Proteins (cerebrospinal fluid)
• Dementia (cerebrospinal fluid, complications, diagnosis)
• Female
• Humans
• Immunoblotting
• Male
• Middle Aged