title: Neurodegenerative disease phenotypes in carriers of MAPT p.A152T, a risk factor for frontotemporal dementia spectrum disorders and Alzheimer disease.
abstract: Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.
authors.affiliation: *Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA †Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, ON, Canada ‡Department of Neurology and Neurosciences, Brain Dynamics Research Center, Dokuz Eylül University, İzmir, Turkey §BEYINMER, Istanbul Kultur University, Istanbul, Turkey ∥Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 'Marqués de Valdecilla' University Hospital, Institute for Formation and Research of the Foundation 'Marqués de Valdecilla' (IFIMAV), University of Cantabria, Cantabria, Spain ¶Cognitive Disorders Unit, Department of Neurology, Hospital Universitario Donostia, San Sebastian, Gipuzkoa, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), area 6, Institute Carlos III, Spain; Neuroscience Area, Institute Biodonostia, San Sebastian, Gipuzkoa, Spain #Department of Neurology, Neurobehavior Division, University of California, Los Angeles **Department of Psychiatry and Neurology, University of California, Los Angeles, CA ††Department of Neuroscience, Mayo Clinic, Rochester, MN ‡‡Department of Medicine, Weill Medical College of Cornell University, New York, NY.
authors.forename: Suzee E
authors.initials: SE
authors.lastname: Lee
authors.forename: Maria C
authors.initials: MC
authors.lastname: Tartaglia
authors.forename: Görsev
authors.initials: G
authors.lastname: Yener
authors.forename: Sermin
authors.initials: S
authors.lastname: Genç
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.forename: Pascual
authors.initials: P
authors.lastname: Sanchez-Juan
authors.forename: Fermin
authors.initials: F
authors.lastname: Moreno
authors.forename: Mario F
authors.initials: MF
authors.lastname: Mendez
authors.forename: Eric
authors.initials: E
authors.lastname: Klein
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.forename: Robert O
authors.initials: RO
authors.lastname: Kenet
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Geschwind
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.forename: Anna M
authors.initials: AM
authors.lastname: Karydas
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D012189:Retrospective Studies; D012307:Risk Factors; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins