title: Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion.
abstract: BACKGROUND
  TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The C9ORF72 hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the C9ORF72 expansion carrier status affects these variables.
  
  
  METHODS
  The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, AΒ1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits.
  
  
  RESULTS
  There was no difference in CSF TDP-43 levels between the C9ORF72 expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort).
  
  
  CONCLUSIONS
  CSF TDP-43 does not seem to distinguish the C9ORF72 expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Junttila
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Kuvaja
authors.affiliation: Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Hartikainen
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Maritta
authors.initials: M
authors.lastname: Siloaho
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Helisalmi
authors.affiliation: Department of Neurology, Oulu University Hospital, Oulu, Finland.
authors.forename: Virpi
authors.initials: V
authors.lastname: Moilanen
authors.affiliation: Research Programs Unit, Molecular Neurology, Biomedicum, University of Helsinki, Helsinki, Finland; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kiviharju
authors.affiliation: Research Programs Unit, Molecular Neurology, Biomedicum, University of Helsinki, Helsinki, Finland; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Lilja
authors.initials: L
authors.lastname: Jansson
authors.affiliation: Research Programs Unit, Molecular Neurology, Biomedicum, University of Helsinki, Helsinki, Finland; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Pentti J
authors.initials: PJ
authors.lastname: Tienari
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Anne Marja
authors.initials: AM
authors.lastname: Remes
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sanna-Kaisa
authors.initials: SK
authors.lastname: Herukka
keywords: Amyotrophic lateral sclerosis; Biomarker; C9ORF72; Cerebrospinal fluid; ELISA; Frontotemporal dementia; Frontotemporal lobar degeneration; TDP-43