TY - JOUR
T1 - Parkinsonism and distinct dementia patterns in a family with the MAPT R406W mutation
AU - Carney, Regina Maria
AU - Kohli, Martin A.
AU - Kunkle, Brian W.
AU - Naj, Adam C.
AU - Gilbert, John
AU - Züchner, Stephan
AU - Pericak-Vance, Margaret A.
N1 - Funding Information:
We are grateful to the families and staff who participated in this study. This work was supported by National Institute of Health grants R01 AG027944 (M. P. V.), U01AG032984 (M. P. V.), Alzheimer's Association grant IIRG09133827 (M. P. V.), American Health Assistance Foundation grant A2011048 (M. P. V.), and a grant from the U.S. Department of Defense ( W81XWH-12-1-0013 ; M. P. V.).
PY - 2014/5
Y1 - 2014/5
N2 - Background: The Arg406Trp (R406W) missense mutation in the microtubule-associated protein-tau gene (MAPT) is a known cause of early-onset dementia. Various dementia phenotypes have been described, including frontotemporal dementia (FTD), FTD with parkinsonism, and early-onset Alzheimer disease (EOAD)-like presentations. Methods: Using whole-exome capture with subsequent sequencing, we identified the R406W mutation in a family with multiple individuals with clinically diagnosed EOAD, in a pattern suggesting autosomal dominant inheritance. We reevaluated all available family members clinically. Results: Each of the affected individuals had a course meeting clinical criteria for EOAD. Two distinct disease trajectories were apparent: one rapidly progressive, and the other long and gradual. Four of five affected individuals also manifested parkinsonian symptoms. FTD features were not prominent and, when present, appeared only late in the course of dementia. Conclusions: The MAPT R406W mutation is associated with EOAD-like symptoms and parkinsonism without FTD, as well as distinct cognitive courses.
AB - Background: The Arg406Trp (R406W) missense mutation in the microtubule-associated protein-tau gene (MAPT) is a known cause of early-onset dementia. Various dementia phenotypes have been described, including frontotemporal dementia (FTD), FTD with parkinsonism, and early-onset Alzheimer disease (EOAD)-like presentations. Methods: Using whole-exome capture with subsequent sequencing, we identified the R406W mutation in a family with multiple individuals with clinically diagnosed EOAD, in a pattern suggesting autosomal dominant inheritance. We reevaluated all available family members clinically. Results: Each of the affected individuals had a course meeting clinical criteria for EOAD. Two distinct disease trajectories were apparent: one rapidly progressive, and the other long and gradual. Four of five affected individuals also manifested parkinsonian symptoms. FTD features were not prominent and, when present, appeared only late in the course of dementia. Conclusions: The MAPT R406W mutation is associated with EOAD-like symptoms and parkinsonism without FTD, as well as distinct cognitive courses.
KW - Dementia
KW - Early-onset Alzheimer's disease
KW - Frontotemporal dementia
KW - Microtubule-associated protein-tau
KW - Whole-exome sequencing
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U2 - 10.1016/j.jalz.2013.02.011
DO - 10.1016/j.jalz.2013.02.011
M3 - Article
C2 - 23727082
AN - SCOPUS:84899636409
VL - 10
SP - 360
EP - 365
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 3
ER -
