title: Association between tau H2 haplotype and age at onset in frontotemporal dementia.
abstract: BACKGROUND
  The frontotemporal dementia (FTD) syndromes have been associated with the microtubule-associated tau protein since tau gene mutations have been demonstrated to be the cause of FTD and parkinsonism linked to chromosome 17. In cases of FTD without tau gene mutations, however, it is unclear whether genetic variability in the tau gene is associated with the development or modulation of FTD.
  
  
  OBJECTIVE
  To determine whether genetic variability in tau and apolipoprotein E (ApoE) modulates and contributes to the development of FTD. Design and Patients The distribution of tau gene haplotypes and the ApoE genotype were investigated in 86 patients with well-characterized FTD and 50 control subjects.
  
  
  RESULTS
  No difference in the distribution of the tau H1 and H2 haplotypes between FTD cases and controls was observed, whereas the ApoE epsilon4 allele was more frequent in FTD cases. The presence of at least 1 tau H2 allele was found to be significantly associated with an earlier age of onset in patients with FTD. The association between the H2 allele and age at onset was not related to family history, clinical presentation, or ApoE genotype.
  
  
  CONCLUSIONS
  These findings support a role of tau protein in modulating disease phenotype by influencing the age at onset in these FTD cases.
authors.affiliation: Brain Repair Centre, Department of Clinical Neurosciences, University of Cambridge, England.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Despina
authors.initials: D
authors.lastname: Yancopoulou
authors.forename: Miho
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sawcer
authors.forename: John R
authors.initials: JR
authors.lastname: Hodges
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
mesh_terms: D017668:Age of Onset; D000368:Aged; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003704:Dementia / Q000145:classification / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D017421:Sequence Analysis / Q000379:methods; D016875:tau Proteins / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D016875:tau Proteins