title: FTDP-17 with Pick body-like inclusions associated with a novel tau mutation, p.E372G.
abstract: Mutations in microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Here, we describe a patient with FTDP-17 and a novel missense mutation in exon 13 of MAPT, p.E372G. We compare clinicopathologic features of this patient to two previously unreported patients with another exon 13 mutation, p.G389R. The patient with the p.E372G mutation was a 40-year-old man with behavioral variant frontotemporal dementia (bvFTD), who subsequently developed agrammatic speech and parkinsonism. One of the FTDP-17 patients with p.G389R mutation presented at age 24 with agrammatic variant of primary progressive aphasia, and subsequently behavioral dysfunction. The other presented at age 53 with bvFTD, followed by agrammatic speech and corticobasal syndrome. Neuropathologic features of FTDP-17 due to p.E372G were similar to those of p.G389R, including tau-immunoreactive Pick body-like neuronal inclusions and swollen, tapering thread-like processes in white matter immunoreactive for 3-repeat and 4-repeat tau. Biochemical analysis of insoluble tau showed similar isoform compositions in p.E372G and p.G389R. Functional studies of the p.E372G mutation showed marked increase in tau filament formation and its reduced ability to promote microtubule assembly. Together these findings indicate that p.E372G is a pathogenic MAPT mutation that causes FTDP-17 similar to p.G389R.
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL.
authors.forename: Pawel
authors.initials: P
authors.lastname: Tacik
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Michael A
authors.initials: MA
authors.lastname: DeTure
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Yari
authors.initials: Y
authors.lastname: Carlomagno
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Wen-Lang
authors.initials: WL
authors.lastname: Lin
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Murray
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Baker
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Josephs
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL.
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL.
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.affiliation: Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Leonard
authors.initials: L
authors.lastname: Petrucelli
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.affiliation: Department of Neurology, Weill Cornell Medicine, New York, NY.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Isaacson
authors.affiliation: Department of Neurology, University of Florida College of Medicine, Gainesville, FL.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Heilman
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kouri
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D055815:Young Adult; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: FTDP-17; MAPT mutations; Pick's disease; frontotemporal dementia; primary progressive aphasia