Genetic screen in a large series of patients with primary progressive aphasia

Eliana Marisa Ramos, Deepika Reddy Dokuru, Victoria Van Berlo, Kevin Wojta, Qing Wang, Alden Y. Huang, Zachary A. Miller, Anna M. Karydas, Eileen H. Bigio, Emily Rogalski, Sandra Weintraub, Benjamin Rader, Bruce L. Miller, Maria Luisa Gorno-Tempini, Marek Marsel Mesulam, Giovanni Coppola*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Introduction: Primary progressive aphasia (PPA) is a neurological syndrome, associated with both frontotemporal dementia and Alzheimer's disease, in which progressive language impairment emerges as the most salient clinical feature during the initial stages of disease. Methods: We screened the main genes associated with Alzheimer's disease and frontotemporal dementia for pathogenic and risk variants in a cohort of 403 PPA cases. Results: In this case series study, 14 (3.5%) cases carried (likely) pathogenic variants: four C9orf72 expansions, nine GRN, and one TARDBP mutation. Rare risk variants, TREM2 R47H and MAPT A152T, were associated with a three- to seven-fold increase in risk for PPA. Discussion: Our results show that while pathogenic variants within the most common dementia genes were rarely associated with PPA, these were found almost exclusively in GRN and C9orf72, suggesting that PPA is more TDP43- than tau-related in our series. This is consistent with the finding that PPA frequency in dominantly inherited dementias is the highest in kindreds with GRN variants.

Original languageEnglish (US)
Pages (from-to)553-560
Number of pages8
JournalAlzheimer's and Dementia
Issue number4
StatePublished - Apr 2019


  • C9orf72
  • GRN
  • Genetics
  • Primary progressive aphasia

ASJC Scopus subject areas

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

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