title: Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal dementia carrying a C9orf72 repeat expansion or a GRN mutation.
abstract: OBJECTIVE
  About a half of patients with frontotemporal dementia (FTD) has deposition of phosphorylated TDP-43 protein (pTDP-43) in the brain. We studied pTDP-43 and total TDP-43 levels in plasma and cerebrospinal fluid (CSF) in healthy controls and patients with FTD, including those carrying a repeat expansion in the C9orf72 gene or a mutation in GRN.
  
  
  METHODS
  We included 88 plasma samples of 10 C9orf72 expansion carriers, 5 GRN mutation carriers, 51 patients with FTD without a known mutation and 22 healthy controls. We also obtained CSF samples from 25 patients with FTD (2 with C9orf72 expansion and 3 with a GRN mutation) and 22 healthy controls. We measured pTDP-43 and total TDP-43 levels using sandwich ELISA.
  
  
  RESULTS
  Patients carrying the C9orf72 repeat expansion or a GRN mutation had significantly higher plasma and CSF levels of pTDP-43 than the remaining patients with FTD (p<0.05). In addition, plasma pTDP-43 levels were higher in patients with FTD carrying a C9orf72 expansion or GRN mutations than in healthy controls (p<0.05).
  
  
  CONCLUSIONS
  Our study shows that plasma pTDP-43 levels may be increased in some genetic forms of FTD known to be associated with TDP-43 proteinopathies.
authors.affiliation: Neurology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, , Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Suárez-Calvet
authors.forename: Oriol
authors.initials: O
authors.lastname: Dols-Icardo
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Valle
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández
authors.forename: Guillermo
authors.initials: G
authors.lastname: Amer
authors.forename: Sofía
authors.initials: S
authors.lastname: Antón-Aguirre
authors.forename: Daniel
authors.initials: D
authors.lastname: Alcolea
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Julie
authors.initials: J
authors.lastname: van der Zee
authors.forename: Lubina
authors.initials: L
authors.lastname: Dillen
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: José Luís
authors.initials: JL
authors.lastname: Molinuevo
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D001921:Brain / Q000378:metabolism; D000073885:C9orf72 Protein; D016022:Case-Control Studies; D042622:DNA Repeat Expansion; D004268:DNA-Binding Proteins / Q000097:blood* / Q000134:cerebrospinal fluid / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057180:Frontotemporal Dementia / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D000077153:Progranulins; D011498:Protein Precursors / Q000235:genetics; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D011498:Protein Precursors; D011506:Proteins
keywords: ALS; CSF; DEMENTIA; FRONTAL LOBE; GENETICS