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

Alzheimer Dis Assoc Disord. Oct-Dec 2013;27(4):302-9. doi: 10.1097/WAD.0b013e31828cc357.

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Female
  • Frontotemporal Dementia / diagnosis
  • Frontotemporal Dementia / genetics*
  • Genetic Variation / genetics
  • Heterozygote*
  • Humans
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / genetics
  • Phenotype*
  • Retrospective Studies
  • Risk Factors
  • tau Proteins / genetics*

Substances

  • MAPT protein, human
  • tau Proteins