A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaques

Ann Neurol. 2004 May;55(5):617-26. doi: 10.1002/ana.20083.


Familial forms of frontotemporal dementia (FTD) with tauopathy are mostly caused by mutations in the gene encoding the microtubule-associated protein tau (MAPT). However, rare forms of familial tauopathy without MAPT mutations have been reported, suggesting other tauopathy-related genetic defects. Interestingly, two presenilin 1 (PS1) mutations (Leu113Pro and insArg352) recently have been associated with familial FTD albeit without neuropathological confirmation. We report here a novel PS1 mutation in a patient with Pick-type tauopathy in the absence of extracellular beta-amyloid deposits. The mutation is predicted to substitute Gly-->Val at codon position 183 (Gly183Val) and to affect the splice signal at the junction of the sixth exon and intron. Further clinical-genetic investigation showed a positive family history of FTD-like dementia and suggested that Gly183Val is associated with a phenotypically heterogeneous neurodegenerative disorder. Our results suggest PS1 as a candidate gene for Pick-type tauopathy without MAPT mutations.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Substitution / genetics
  • Amyloid beta-Peptides / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Pedigree
  • Pick Disease of the Brain / genetics*
  • Pick Disease of the Brain / pathology*
  • Plaque, Amyloid / genetics*
  • Plaque, Amyloid / pathology
  • Presenilin-1


  • Amyloid beta-Peptides
  • Membrane Proteins
  • PSEN1 protein, human
  • Presenilin-1