TDP-43 in Cerebrospinal Fluid of Patients With Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

• Published in: Archives of neurology (Chicago) Vol. 65; no. 11; pp. 1481 - 1487
• Main Authors: Steinacker, Petra, Hendrich, Corinna, Sperfeld, Anne D, Jesse, Sarah, von Arnim, Christine A. F, Lehnert, Stefan, Pabst, Alice, Uttner, Ingo, Tumani, Hayrettin, Lee, Virginia M.-Y, Trojanowski, John Q, Kretzschmar, Hans A, Ludolph, Albert, Neumann, Manuela, Otto, Markus
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.11.2008
• Subjects: Adult; Aged; Aged, 80 and over; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - cerebrospinal fluid; Amyotrophic Lateral Sclerosis - complications; Amyotrophic Lateral Sclerosis - diagnosis; Amyotrophic Lateral Sclerosis - psychology; Binding sites; Biological and medical sciences; Biomarkers - cerebrospinal fluid; Body fluids; Brain; Dementia - cerebrospinal fluid; Dementia - complications; Dementia - diagnosis; DNA-Binding Proteins - cerebrospinal fluid; Female; Genotype & phenotype; Humans; Immunoblotting; Immunoglobulins; Male; Medical sciences; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Proteins; Human; Nervous system diseases; Central nervous system disease; Amyotrophic lateral sclerosis; Degenerative disease; Degeneration; Cerebrospinal fluid; Spinal cord disease
• ISSN: 0003-9942; 2168-6149; 1538-3687; 2168-6157
• DOI: 10.1001/archneur.65.11.1481

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.Arch Neurol. 2008;65(11):1481-1487-->