Original Article

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

  1. Bart Dermaut MD, PhD1,
  2. Samir Kumar-Singh MD, PhD1,
  3. Sebastian Engelborghs MD2,3,
  4. Jessie Theuns PhD1,
  5. Rosa Rademakers MSc1,
  6. Jos Saerens MSc3,
  7. Barbara A. Pickut MD3,
  8. Karin Peeters1,
  9. Marleen Van Den Broeck1,
  10. Krist'l Vennekens1,
  11. Stephen Claes MD, PhD1,
  12. Marc Cruts PhD1,
  13. Patrick Cras MD, PhD4,
  14. Jean-Jacques Martin MD, PhD5,
  15. Christine Van Broeckhoven PhD, DSc1,*,
  16. Peter Paul De Deyn MD, PhD2,3

Article first published online: 26 APR 2004

DOI: 10.1002/ana.20083

Issue

Annals of Neurology

Annals of Neurology

Volume 55, Issue 5, pages 617–626, May 2004

Additional Information

How to Cite

Dermaut, B., Kumar-Singh, S., Engelborghs, S., Theuns, J., Rademakers, R., Saerens, J., Pickut, B. A., Peeters, K., Van Den Broeck, M., Vennekens, K., Claes, S., Cruts, M., Cras, P., Martin, J.-J., Van Broeckhoven, C. and De Deyn, P. P. (2004), A novel presenilin 1 mutation associated with Pick's disease but not β-amyloid plaques. Ann Neurol., 55: 617–626. doi: 10.1002/ana.20083

Author Information

  1. 1

    Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium

  2. 2

    Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Born-Bunge Foundation, University of Antwerp, Antwerpen, Belgium

  3. 3

    Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium

  4. 4

    Laboratory of Neurobiology, Born Bunge Foundation, University of Antwerp, Antwerpen, Belgium

  5. 5

    Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, Antwerpen, Belgium

*Department of Molecular Genetics (VIB8), University of Antwerp, Universiteitsplein 1, B-2610, Antwerpen, Belgium

Publication History

  1. Issue published online: 26 APR 2004
  2. Article first published online: 26 APR 2004
  3. Manuscript Accepted: 28 JAN 2004
  4. Manuscript Revised: 27 JAN 2004
  5. Manuscript Received: 24 OCT 2003

Funded by

  • Neurosearch Antwerp
  • Special Research Fund of the University of Antwerp
  • Fund for Scientific Research–Flanders (FWO-F)
  • Medical Foundation Queen Elisabeth
  • International Alzheimer Research Foundation
  • Interuniversity Attraction Poles program P5/19 of the Belgian Federal Science Policy Office, Belgium
  • Alzheimer Association, USA

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Abstract

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.

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