Phenotypic correlations in FTDP-17

Lee A. Reed, Zbigniew K. Wszolek, Mike Hutton

Research output: Contribution to journalComment/debatepeer-review

185 Scopus citations


Frontotemporal dementias with parkinsonism linked to chromosome 17 (FTDP-17) are hereditary tauopathies affecting at least 50 known kindred worldwide. Most kindred present with severe behavioral or psychiatric manifestations progressing to dementia, while some kindred first manifest a parkinsonian-plus syndrome. Nine missense mutations, one deletion mutation, and two transition mutations not altering the encoded amino acid, have been described in or near the microtubule-binding domains within exons 9, 10, 12, and 13. In addition, five different intronic mutations have been reported in the 5′ splice-site of the alternatively spliced exon 10. Missense mutations affecting constitutively expressed exons affect all six major tau isoforms and result in neurofibrillary tangles similar to those present in secondary tauopathies, such as Alzheimer's disease. In contrast, mutations that affect the alternatively spliced exon 10 or its 5′ splice regulatory region alter the ratio of the tau isoforms incorporated into the tangles and result in filamentous inclusions resembling those seen in the primary tauopathies, such as progressive supranuclear palsy, corticobasal degeneration, and Pick's disease. The severity and heterogeneity of the clinicomorphologic phenotype may, in part, reflect the diversity in the primary molecular mechanisms of disease in FTDP-17.

Original languageEnglish (US)
Pages (from-to)89-107
Number of pages19
JournalNeurobiology of aging
Issue number1
StatePublished - 2001


  • Alternative splicing
  • FTDP-17
  • Frontotemporal dementia
  • Hereditary neurodegenerative disease
  • Parkinsonism
  • Tau

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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