Parkinsonism and distinct dementia patterns in a family with the MAPT R406W mutation

Regina Maria Carney, Martin A. Kohli, Brian W. Kunkle, Adam C. Naj, John Gilbert, Stephan Züchner, Margaret A. Pericak-Vance

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background: The Arg406Trp (R406W) missense mutation in the microtubule-associated protein-tau gene (MAPT) is a known cause of early-onset dementia. Various dementia phenotypes have been described, including frontotemporal dementia (FTD), FTD with parkinsonism, and early-onset Alzheimer disease (EOAD)-like presentations. Methods: Using whole-exome capture with subsequent sequencing, we identified the R406W mutation in a family with multiple individuals with clinically diagnosed EOAD, in a pattern suggesting autosomal dominant inheritance. We reevaluated all available family members clinically. Results: Each of the affected individuals had a course meeting clinical criteria for EOAD. Two distinct disease trajectories were apparent: one rapidly progressive, and the other long and gradual. Four of five affected individuals also manifested parkinsonian symptoms. FTD features were not prominent and, when present, appeared only late in the course of dementia. Conclusions: The MAPT R406W mutation is associated with EOAD-like symptoms and parkinsonism without FTD, as well as distinct cognitive courses.

Original languageEnglish (US)
Pages (from-to)360-365
Number of pages6
JournalAlzheimer's and Dementia
Issue number3
StatePublished - May 2014


  • Dementia
  • Early-onset Alzheimer's disease
  • Frontotemporal dementia
  • Microtubule-associated protein-tau
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy
  • Medicine(all)


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