title: Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17.
abstract: Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Over 10 exonic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brains of FTDP-17 patients indicated that different pathogenic mutations differentially altered distinct biochemical properties and stoichiometry of brain tau isoforms. Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in disease pathogenesis by reducing the ability of tau to bind microtubules and promote microtubule assembly.
authors.affiliation: Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hong
authors.forename: V
authors.initials: V
authors.lastname: Zhukareva
authors.forename: V
authors.initials: V
authors.lastname: Vogelsberg-Ragaglia
authors.forename: Z
authors.initials: Z
authors.lastname: Wszolek
authors.forename: L
authors.initials: L
authors.lastname: Reed
authors.forename: B I
authors.initials: BI
authors.lastname: Miller
authors.forename: D H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: T D
authors.initials: TD
authors.lastname: Bird
authors.forename: D
authors.initials: D
authors.lastname: McKeel
authors.forename: A
authors.initials: A
authors.lastname: Goate
authors.forename: J C
authors.initials: JC
authors.lastname: Morris
authors.forename: K C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.forename: G D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
mesh_terms: D017398:Alternative Splicing; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17; D003704:Dementia / Q000235:genetics* / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation; D020125:Mutation, Missense; D010302:Parkinson Disease, Secondary / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D013577:Syndrome; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D011994:Recombinant Proteins; D016875:tau Proteins