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

Research output: Contribution to journalArticle

Abstract

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
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

Primary Progressive Aphasia
Frontotemporal Dementia
Alzheimer Disease
Dementia
Genes
Language
Mutation

Keywords

  • C9orf72
  • GRN
  • Genetics
  • Primary progressive aphasia
  • TARDBP

ASJC Scopus subject areas

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

Cite this

Ramos, E. M., Dokuru, D. R., Van Berlo, V., Wojta, K., Wang, Q., Huang, A. Y., ... Coppola, G. (2019). Genetic screen in a large series of patients with primary progressive aphasia. Alzheimer's and Dementia, 15(4), 553-560. https://doi.org/10.1016/j.jalz.2018.10.009
Ramos, Eliana Marisa ; Dokuru, Deepika Reddy ; Van Berlo, Victoria ; Wojta, Kevin ; Wang, Qing ; Huang, Alden Y. ; Miller, Zachary A. ; Karydas, Anna M. ; Bigio, Eileen H ; Rogalski, Emily ; Weintraub, Sandra ; Rader, Benjamin ; Miller, Bruce L. ; Gorno-Tempini, Maria Luisa ; Mesulam, Marek-Marsel ; Coppola, Giovanni. / Genetic screen in a large series of patients with primary progressive aphasia. In: Alzheimer's and Dementia. 2019 ; Vol. 15, No. 4. pp. 553-560.
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Ramos, EM, Dokuru, DR, Van Berlo, V, Wojta, K, Wang, Q, Huang, AY, Miller, ZA, Karydas, AM, Bigio, EH, Rogalski, E, Weintraub, S, Rader, B, Miller, BL, Gorno-Tempini, ML, Mesulam, M-M & Coppola, G 2019, 'Genetic screen in a large series of patients with primary progressive aphasia', Alzheimer's and Dementia, vol. 15, no. 4, pp. 553-560. https://doi.org/10.1016/j.jalz.2018.10.009

Genetic screen in a large series of patients with primary progressive aphasia. / Ramos, Eliana Marisa; Dokuru, Deepika Reddy; Van Berlo, Victoria; Wojta, Kevin; Wang, Qing; Huang, Alden Y.; Miller, Zachary A.; Karydas, Anna M.; Bigio, Eileen H; Rogalski, Emily; Weintraub, Sandra; Rader, Benjamin; Miller, Bruce L.; Gorno-Tempini, Maria Luisa; Mesulam, Marek-Marsel; Coppola, Giovanni.

In: Alzheimer's and Dementia, Vol. 15, No. 4, 01.04.2019, p. 553-560.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic screen in a large series of patients with primary progressive aphasia

AU - Ramos, Eliana Marisa

AU - Dokuru, Deepika Reddy

AU - Van Berlo, Victoria

AU - Wojta, Kevin

AU - Wang, Qing

AU - Huang, Alden Y.

AU - Miller, Zachary A.

AU - Karydas, Anna M.

AU - Bigio, Eileen H

AU - Rogalski, Emily

AU - Weintraub, Sandra

AU - Rader, Benjamin

AU - Miller, Bruce L.

AU - Gorno-Tempini, Maria Luisa

AU - Mesulam, Marek-Marsel

AU - Coppola, Giovanni

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

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KW - Primary progressive aphasia

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Ramos EM, Dokuru DR, Van Berlo V, Wojta K, Wang Q, Huang AY et al. Genetic screen in a large series of patients with primary progressive aphasia. Alzheimer's and Dementia. 2019 Apr 1;15(4):553-560. https://doi.org/10.1016/j.jalz.2018.10.009