title: Young-onset frontotemporal dementia in a homozygous tau R406W mutation carrier.
abstract: Microtubule-associated protein tau mutations result in 10-20% of cases of genetic frontotemporal lobar degeneration. Tau mutation carriers typically develop behavioral variant frontotemporal dementia with or without parkinsonism. Unlike most frontotemporal dementia gene mutations, heterozygous R406W tau mutation carriers most often develop clinical Alzheimer's disease. We report a homozygous tau R406W mutation carrier with behavioral variant frontotemporal dementia who developed symptoms 20 years before mean family symptom onset. Voxel-based morphometry showed frontoinsular, frontal, and mesial temporal cortical atrophy. Homozygous tau R406W mutations appear to accelerate symptom onset and drive a behavioral variant frontotemporal dementia syndrome.
authors.affiliation: Department of Neurology National Neuroscience Institute Tan Tock Seng Hospital Novena Singapore 308433; Memory and Aging Centre Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Adeline S L
authors.initials: AS
authors.lastname: Ng
authors.affiliation: Memory and Aging Centre Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Sias
authors.affiliation: Memory and Aging Centre Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Pressman
authors.affiliation: Memory and Aging Centre Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Fong
authors.affiliation: Memory and Aging Centre Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Karydas
authors.affiliation: Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Zanto
authors.affiliation: Memory and Aging Centre Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Mary
authors.initials: M
authors.lastname: De May
authors.affiliation: David Geffen School of Medicine University of California, Los Angeles Los Angeles California 90095.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: David Geffen School of Medicine University of California, Los Angeles Los Angeles California 90095.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.affiliation: Memory and Aging Centre Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Memory and Aging Centre Department of Neurology University of California, San Francisco San Francisco California 94158.
authors.forename: Suzee E
authors.initials: SE
authors.lastname: Lee