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Petra Steinacker, PhD; Corinna Hendrich, MD; Anne D. Sperfeld, MD; Sarah Jesse, MD; Christine A. F. von Arnim, MD; Stefan Lehnert, PhD; Alice Pabst; Ingo Uttner, PhD; Hayrettin Tumani, MD; Virginia M.-Y. Lee, PhD; John Q. Trojanowski, MD, PhD; Hans A. Kretzschmar, MD; Albert Ludolph, MD; Manuela Neumann, MD; Markus Otto, MD

Arch Neurol. 2008;65(11):1481-1487.

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.

Author Affiliations: Department of Neurology, University of Ulm, Ulm (Drs Steinacker, Hendrich, Sperfeld, Jesse, von Arnim, Lehnert, Uttner, Tumani, Ludolph, and Otto and Ms Pabst), and Center for Neuropathology and Prion Research, Ludwig-Maximilians University Munich, Munich (Drs Kretzschmar and Neumann), Germany; and Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Alzheimer's Disease Core Center, Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia (Drs Lee and Trojanowski).

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