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Research paper
Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal dementia carrying a C9orf72 repeat expansion or a GRN mutation
  1. Marc Suárez-Calvet1,2,
  2. Oriol Dols-Icardo1,2,
  3. Albert Lladó3,
  4. Raquel Sánchez-Valle3,
  5. Isabel Hernández4,
  6. Guillermo Amer5,
  7. Sofía Antón-Aguirre1,2,
  8. Daniel Alcolea1,2,
  9. Juan Fortea1,2,
  10. Isidre Ferrer2,6,
  11. Julie van der Zee7,8,
  12. Lubina Dillen7,8,
  13. Christine Van Broeckhoven7,8,
  14. José Luís Molinuevo3,
  15. Rafael Blesa1,2,
  16. Jordi Clarimón1,2,
  17. Alberto Lleó1,2
  1. 1Neurology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
  2. 2Center for Networker Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
  3. 3Department of Neurology, Alzheimer's Disease and other Cognitive Disorders Unit, Hospital Clínic, Barcelona, Spain
  4. 4Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain
  5. 5Neurology Department, Hospital Universitari Son Espases, Majorca, Spain
  6. 6Institut de Neuropatología, Servei Anatomia Patológica, IDIBELL, Hospital Universitari de Bellvitge, University of Barcelona, Barcelona, Spain
  7. 7Department of Molecular Genetics, Neurodegenerative Brain Disease Group, VIB, Antwerp, Belgium
  8. 8Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
  1. Correspondence to Dr Alberto Lleó, Neurology Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni M Claret 167, Barcelona 08025, Spain; alleo{at}santpau.es

Abstract

Objectives 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.

  • DEMENTIA
  • ALS
  • CSF
  • FRONTAL LOBE
  • GENETICS

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