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 language | English (US) |
|---|---|
| Pages (from-to) | 553-560 |
| Number of pages | 8 |
| Journal | Alzheimer's and Dementia |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2019 |
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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
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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 journal › Article
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.
AB - 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.
KW - C9orf72
KW - GRN
KW - Genetics
KW - Primary progressive aphasia
KW - TARDBP
UR - http://www.scopus.com/inward/record.url?scp=85060338124&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060338124&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2018.10.009
DO - 10.1016/j.jalz.2018.10.009
M3 - Article
C2 - 30599136
AN - SCOPUS:85060338124
VL - 15
SP - 553
EP - 560
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 4
ER -