Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau

Orso Bugiani, Jill R. Murrell, Giorgio Giaccone, Masato Hasegawa, Giuseppe Ghigo, Massimo Tabaton, Michela Morbin, Alberto Primavera, Francesco Carella, Claudio Solaro, Marina Grisoli, Mario Savoiardo, Maria Grazia Spillantini, Fabrizio Tagliavini, Michel Goedert, Bernardino Ghetti

Research output: Contribution to journalArticle

302 Scopus citations

Abstract

The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17. Exonic and intronic mutations have been described in a number of families. Here we describe a P301S mutation in exon 10 of the tau gene in a new family. Two members of this family were affected. One individual presented with frontotemporal dementia, whereas his son has corticobasal degeneration, demonstrating that the same primary gene defect in tau can lead to 2 distinct clinical phenotypes. Both individuals developed rapidly progressive disease in the third decade. Neuropathologically, the father presented with an extensive filamentous pathology made of hyperphosphorylated tau protein. Biochemically, recombinant tau protein with the P301S mutation showed a greatly reduced ability to promote microtubule assembly.

Original languageEnglish (US)
Pages (from-to)667-677
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume58
Issue number6
DOIs
StatePublished - Jun 1999

Keywords

  • Cytoskeleton
  • Dementia
  • Mutation
  • Neurodegenerative Disease
  • Tau proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau'. Together they form a unique fingerprint.

  • Cite this

    Bugiani, O., Murrell, J. R., Giaccone, G., Hasegawa, M., Ghigo, G., Tabaton, M., Morbin, M., Primavera, A., Carella, F., Solaro, C., Grisoli, M., Savoiardo, M., Spillantini, M. G., Tagliavini, F., Goedert, M., & Ghetti, B. (1999). Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. Journal of Neuropathology and Experimental Neurology, 58(6), 667-677. https://doi.org/10.1097/00005072-199906000-00011