Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal dementia carrying a C9orf72 repeat expansion or a GRN mutation

J Neurol Neurosurg Psychiatry. 2014 Jun;85(6):684-91. doi: 10.1136/jnnp-2013-305972. Epub 2013 Dec 4.


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.


Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blotting, Southern
  • Brain / metabolism
  • C9orf72 Protein
  • Case-Control Studies
  • DNA Repeat Expansion*
  • DNA-Binding Proteins / blood*
  • DNA-Binding Proteins / cerebrospinal fluid
  • DNA-Binding Proteins / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Frontotemporal Dementia / blood*
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / metabolism
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Phosphorylation
  • Progranulins
  • Protein Precursors / genetics
  • Proteins / genetics*


  • C9orf72 Protein
  • C9orf72 protein, human
  • DNA-Binding Proteins
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Protein Precursors
  • Proteins