Neurodegenerative disease phenotypes in carriers of MAPT P.A152T, a risk factor for frontotemporal dementia spectrum disorders and alzheimer disease

Suzee E. Lee, Maria C. Tartaglia, Görsev Yener, Sermin Genç, William W. Seeley, Pascual Sanchez-Juan, Fermin Moreno, Mario F. Mendez, Eric Klein, Rosa Rademakers, Adolfo López De Munain, Onofre Combarros, Joel H. Kramer, Robert O. Kenet, Adam L. Boxer, Michael D. Geschwind, Maria Luisa Gorno-Tempini, Anna M. Karydas, Gil D. Rabinovici, Giovanni CoppolaDaniel H. Geschwind, Bruce L. Miller

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.

Original languageEnglish (US)
Pages (from-to)302-309
Number of pages8
JournalAlzheimer disease and associated disorders
Volume27
Issue number4
DOIs
StatePublished - Oct 1 2013

Keywords

  • Alzheimer disease
  • all cognitive disorders/dementia
  • corticobasal degeneration
  • frontotemporal dementia
  • progressive supranuclear palsy

ASJC Scopus subject areas

  • Clinical Psychology
  • Gerontology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Lee, S. E., Tartaglia, M. C., Yener, G., Genç, S., Seeley, W. W., Sanchez-Juan, P., Moreno, F., Mendez, M. F., Klein, E., Rademakers, R., Munain, A. L. D., Combarros, O., Kramer, J. H., Kenet, R. O., Boxer, A. L., Geschwind, M. D., Gorno-Tempini, M. L., Karydas, A. M., Rabinovici, G. D., ... Miller, B. L. (2013). Neurodegenerative disease phenotypes in carriers of MAPT P.A152T, a risk factor for frontotemporal dementia spectrum disorders and alzheimer disease. Alzheimer disease and associated disorders, 27(4), 302-309. https://doi.org/10.1097/WAD.0b013e31828cc357