Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia

Ann Neurol. 2016 Sep;80(3):472-6. doi: 10.1002/ana.24731. Epub 2016 Aug 10.

Abstract

Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long-term potentiation-like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short-interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal-dominant FTD. Ann Neurol 2016;80:472-476.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • C9orf72 Protein
  • Cerebral Cortex / physiopathology*
  • Female
  • Frontotemporal Dementia / genetics
  • Frontotemporal Dementia / physiopathology*
  • Heterozygote
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Long-Term Potentiation / physiology*
  • Male
  • Middle Aged
  • Prodromal Symptoms*
  • Progranulins
  • Proteins / genetics
  • Single-Blind Method
  • Transcranial Magnetic Stimulation / methods*

Substances

  • Biomarkers
  • C9orf72 Protein
  • C9orf72 protein, human
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Proteins