title: 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.
  
  
  OBJECTIVE
  To examine TDP-43 in cerebrospinal fluid (CSF) and to analyze whether it could serve as a diagnostic marker.
  
  
  METHODS
  We characterized CSF TDP-43 by immunoblot using different TDP-43 antibodies and determined the relative TDP-43 levels in CSF samples from patients.
  
  
  METHODS
  Academic research.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Steinacker
authors.forename: Corinna
authors.initials: C
authors.lastname: Hendrich
authors.forename: Anne D
authors.initials: AD
authors.lastname: Sperfeld
authors.forename: Sarah
authors.initials: S
authors.lastname: Jesse
authors.forename: Christine A F
authors.initials: CA
authors.lastname: von Arnim
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehnert
authors.forename: Alice
authors.initials: A
authors.lastname: Pabst
authors.forename: Ingo
authors.initials: I
authors.lastname: Uttner
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Tumani
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Albert
authors.initials: A
authors.lastname: Ludolph
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis* / Q000523:psychology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004268:DNA-Binding Proteins / Q000134:cerebrospinal fluid*; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins