A Novel Presenilin 1 Mutation Associated with Pick's Disease but Not β-Amyloid Plaques

Bart Dermaut, Samir Kumar-Singh, Sebastian Engelborghs, Jessie Theuns, Rosa Rademakers, Jos Saerens, Barbara A. Pickut, Karin Peeters, Marleen Van Den Broeck, Krist'l Vennekens, Stephen Claes, Marc Cruts, Patrick Cras, Jean Jacques Martin, Christine Van Broeckhoven, Peter Paul De Deyn

Research output: Contribution to journalArticlepeer-review

172 Scopus citations


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 β-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.

Original languageEnglish (US)
Pages (from-to)617-626
Number of pages10
JournalAnnals of neurology
Issue number5
StatePublished - May 1 2004

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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