title: Novel G335V mutation in the tau gene associated with early onset familial frontotemporal dementia.
abstract: Mutations in the tau gene cause familial frontotemporal dementia and parkinsonism linked to chromosome 17. Here we describe a novel missense mutation in exon 12 of the tau gene, G335V, in a German family with frontotemporal dementia of early age at onset, in the third decade of life. Functional analysis of recombinant tau protein with the G335V mutation showed a dramatically reduced ability to promote microtubule assembly and a more rapid and accelerated tau filament formation, suggesting that the primary effect of the mutation might be the provision of a pool of unbound tau making it available for aberrant tau aggregation.
authors.affiliation: Center for Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
authors.forename: Silvia
authors.initials: S
authors.lastname: Diekmann
authors.forename: Uwe
authors.initials: U
authors.lastname: Bertsch
authors.forename: Ben
authors.initials: B
authors.lastname: Vanmassenhove
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
mesh_terms: D017668:Age of Onset; D000925:Anticoagulants; D003704:Dementia / Q000235:genetics*; D005192:Family Health; D005260:Female; D005858:Germany; D006493:Heparin; D006801:Humans; D008297:Male; D008870:Microtubules / Q000378:metabolism; D020125:Mutation, Missense; D010375:Pedigree; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D011994:Recombinant Proteins; D016875:tau Proteins; D006493:Heparin